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_001754.5(RUNX1):c.990C>T (p.Phe330=)

CA512341388

1587386 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 9583288a-843b-4639-a2eb-226cf1bacb3c

Approved on: 2026-04-29

Published on: 2026-04-29

HGVS expressions

NM_001754.5(RUNX1):c.990C>T (p.Phe330=)

NM_001754.5:c.990C>T

NC_000021.9:g.34792588G>A

CM000683.2:g.34792588G>A

NC_000021.8:g.36164885G>A

CM000683.1:g.36164885G>A

NC_000021.7:g.35086755G>A

NG_011402.2:g.1197124C>T

ENST00000675419.1:c.990C>T

ENST00000300305.7:c.990C>T

ENST00000344691.8:c.909C>T

ENST00000399240.5:c.717C>T

ENST00000437180.5:c.990C>T

ENST00000482318.5:c.*580C>T

NM_001001890.2:c.909C>T

NM_001754.4:c.990C>T

NM_001001890.3:c.909C>T

Likely Benign

BP4 BP7 PM2_Supporting

PM1 PM5 PM3 PM4 PM6 BS2 BS1 BS4 BS3 PVS1 PS2 PS4 PS3 PS1 BP2 BP3 BP1 BP5 BA1 PP1 PP4 PP3 PP2

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RUNX1 Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.990C>T (p.Phe330=) is a synonymous variant which has a SpliceAI score ≤ 0.20 (0.0) (BP4, BP7). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.

BP4

This synonymous variant has a SpliceAI score ≤ 0.20 (0).

BP7

This synonymous variant has a SpliceAI score ≤ 0.20 (0)

PM2_Supporting

This variant has a MAF ≤ 0.00005 in gnomAD v4.0 in all subpopulations with at least 20X coverage for RUNX1 (PM2_supporting).

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 NOR is it within residues 89-204

PM5

This is not a missense variant, and there has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM3

This rule is not applicable for the MM-VCEP

PM4

This variant is not an inframe indel

PM6

This variant has not been reported in probands in the literature.

BS2

This rule is not applicable for the MM-VCEP

BS1

Highest MAF of 0.00004(0.004%) in South Asian population in gnomAD v4.0.0 is less than 0.00015 (0.015%)

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

PVS1

This variant is not a null variant, as it does not impact any of the following processes or sites: Nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single exon deletion, multiple exon deletions

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS4

This variant has not been reported in probands.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS1

This is not a missense variant, and there has not yet been an amino acid change determined to be pathogenic at this amino acid residue.

BP2

This variant has not been detected in a homozygous state in an individual or in a population database (gnomAD).

BP3

This rule is not applicable for the MM-VCEP

BP1

This rule is not applicable for the MM-VCEP

BP5

This rule is not applicable for the MM-VCEP

BA1

Highest MAF is less than 0.0015 (0.15%) at 0.00004(0.004%, 4 allele count/ 88648 allele number) in the South Asian subpopulation of gnomAD v4.0.0 cohort

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP4

This rule is not applicable for the MM-VCEP

PP3

This synonymous variant does not have a SpliceAI score of ≥ 0.38 (0).

PP2

This rule is not applicable for the MM-VCEP

Curation History

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