Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • See Evidence submitted by expert panel for details.

Variant: NM_004958.3:c.997C>T

CA416041964

1296991 (ClinVar)

Gene: MTOR
Condition: overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: 8bc13dd2-4dbf-47b4-8467-bac6941bfdf9

HGVS expressions

NM_004958.3:c.997C>T
NC_000001.11:g.11247938G>A
CM000663.2:g.11247938G>A
NC_000001.10:g.11307995G>A
CM000663.1:g.11307995G>A
NC_000001.9:g.11230582G>A
NG_033239.1:g.19614C>T
ENST00000361445.9:c.997C>T
ENST00000361445.8:c.997C>T
NM_004958.4:c.997C>T
NM_001386500.1:c.997C>T
NM_001386501.1:c.-143C>T
NM_004958.4(MTOR):c.997C>T (p.Leu333=)

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 24
PM3 PM1 PM4 PM5 PM6 PS2 PS4 PS3 PS1 BA1 PVS1 BP2 BP3 BP1 BP5 BP7 BS2 BS4 BS3 BS1 PP4 PP1 PP3 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.997C>T (NM_004958.4) variant in MTOR is a synonymous (silent) variant in MTOR. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as Uncertain significance for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: PM2_P, BP4; 0 points (VCEP specifications version 1; Approved: 1/31/2021)
Met criteria codes
BP4
No predicted effect on splicing per varSEAK, spliceAI and MaxEntScan.
PM2_Supporting
present in 1 European (non-Finnish) exome in gnomAD
Not Met criteria codes
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Highly conserved nucleotide
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2022-02-17
Published on: 2022-02-17
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