3-129061809-TGTAC-GTGGG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate

The NM_000174.5(GP9):​c.70_74delTGTACinsGTGGG​(p.CysThr24ValGly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GP9
NM_000174.5 missense

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.46
Variant links:
Genes affected
GP9 (HGNC:4444): (glycoprotein IX platelet) This gene encodes a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib, a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor. The complete receptor complex includes noncovalent association of the alpha and beta subunits with the protein encoded by this gene and platelet glycoprotein V. Defects in this gene are a cause of Bernard-Soulier syndrome, also known as giant platelet disease. These patients have unusually large platelets and have a clinical bleeding tendency. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a chain Platelet glycoprotein IX (size 160) in uniprot entity GPIX_HUMAN there are 24 pathogenic changes around while only 0 benign (100%) in NM_000174.5
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-129061809-TGTAC-GTGGG is Pathogenic according to our data. Variant chr3-129061809-TGTAC-GTGGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3588369.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GP9NM_000174.5 linkc.70_74delTGTACinsGTGGG p.CysThr24ValGly missense_variant ENST00000307395.5 NP_000165.1 P14770
GP9XM_047447997.1 linkc.70_74delTGTACinsGTGGG p.CysThr24ValGly missense_variant XP_047303953.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GP9ENST00000307395.5 linkc.70_74delTGTACinsGTGGG p.CysThr24ValGly missense_variant 1 NM_000174.5 ENSP00000303942.4 P14770

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Bernard Soulier syndrome Pathogenic:1
Feb 16, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-128780652; API