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_000212.3(ITGB3):c.414G>C (p.Val138=)

CA8622959

701285 (ClinVar)

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 8d9f3ce9-f94c-4ca3-973c-a26a6a6968d4

Approved on: 2023-08-15

Published on: 2026-08-07

HGVS expressions

NM_000212.3(ITGB3):c.414G>C (p.Val138=)

NM_000212.3:c.414G>C

NC_000017.11:g.47284495G>C

CM000679.2:g.47284495G>C

NC_000017.10:g.45361861G>C

CM000679.1:g.45361861G>C

NC_000017.9:g.42716860G>C

NG_008332.2:g.35654G>C

ENST00000696963.1:c.414G>C

ENST00000559488.7:c.414G>C

ENST00000559488.5:c.414G>C

ENST00000560629.1:c.379G>C

ENST00000571680.1:c.414G>C

NM_000212.2:c.414G>C

Likely Benign

BP7 BP4 PM2_Supporting

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.414G>C (p.Val138=), no individuals with glanzmann thrombasthenia were reported with the variant. The highest population minor allele frequency in gnomAD v4.1 is 8.475e-7 (1/1179980 alleles) in the European (Non-Finnish) genetic ancestry group which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of -.103 shows that the nucleotide position is not highly conserved (BP4, BP7). Due to conflicting evidence, this variant is classified as likely benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting, BP4, BP7. (PD VCEP specifications version 2.1).

BP7

The c.414G>C (p.Val138=) variant is a synonymous that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of -.103 (BP7).

BP4

The c.414G>C (p.Val138=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.1 is 8.475e-7 (1/1179980 alleles) in the European (Non-Finnish) genetic ancestry group which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).

Curation History

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