Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001164508.2(NEB):c.18464A>C (p.Tyr6155Ser)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA1907955

385695 (ClinVar)

Gene: NEB

Condition: nemaline myopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 475d74fb-383a-4125-b6e5-33360f6fe82e

Approved on: 2024-08-07

Published on: 2024-10-01

HGVS expressions

NM_001164508.2:c.18464A>C

NM_001164508.2(NEB):c.18464A>C (p.Tyr6155Ser)

NC_000002.12:g.151565051T>G

CM000664.2:g.151565051T>G

NC_000002.11:g.152421565T>G

CM000664.1:g.152421565T>G

NC_000002.10:g.152129811T>G

NG_009382.2:g.174437A>C

ENST00000690043.1:c.1315A>C

ENST00000397345.8:c.18464A>C

ENST00000427231.7:c.18464A>C

ENST00000172853.14:c.13361A>C

ENST00000397345.7:c.18464A>C

ENST00000409198.5:c.13361A>C

ENST00000413693.5:c.2654A>C

ENST00000427231.6:c.18464A>C

ENST00000603639.5:c.18464A>C

ENST00000604864.5:c.18464A>C

ENST00000618972.4:c.18464A>C

NM_001164507.1:c.18464A>C

NM_001164508.1:c.18464A>C

NM_001271208.1:c.18464A>C

NM_004543.4:c.13361A>C

NM_001271208.2:c.18464A>C

NM_004543.5:c.13361A>C

NM_001164507.2:c.18464A>C

Likely Benign

BS1

BP4 PP3 PM2 BA1

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for NEB Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The c.18464A>C (p.Tyr6155Ser) variant in NEB is a missense variant predicted to cause substitution of tyrosine by serine at amino acid 6155. The highest population filtering allele frequency in gnomAD v4.1.0 is 0.004863 (391/73822 alleles, 3 homozygotes) in the African/African American population, which is higher than the ClinGen Congenital Myopathies VCEP threshold (MAF≥0.000237) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.271, which is neither above nor below the thresholds predicting a damaging or benign impact on NEB function. In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive nemaline myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BS1. (Congenital Myopathies VCEP specifications version 1; 8/7/2024)

BS1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.004863 (391/73822 alleles, 3 homozygotes) in the African/African American population, which is higher than the ClinGen Congenital Myopathies VCEP threshold (MAF ≥ 0.000237) for BS1, and therefore meets this criterion

BP4

The computational predictor REVEL gives a score of 0.271, which is neither above nor below the thresholds predicting a damaging or benign impact on NEB function.

PP3

The computational predictor REVEL gives a score of 0.271, which is neither above nor below the thresholds predicting a damaging or benign impact on NEB function.

PM2

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.004863 (391/73822 alleles, 3 homozygotes) in the African/African American population

BA1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.004863 (391/73822 alleles, 3 homozygotes) in the African/African American population

Curation History

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