3-129061809-TGTAC-GTGGG

Variant names:

• chr3-129061809-TGTAC-GTGGG
• NM_000174.5:c.70_74delTGTACinsGTGGG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP5_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
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.46

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]

ACMG classification

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
GP9	NM_000174.5	c.70_74delTGTACinsGTGGG	p.CysThr24ValGly	missense_variant		ENST00000307395.5	NP_000165.1
GP9	XM_047447997.1	c.70_74delTGTACinsGTGGG	p.CysThr24ValGly	missense_variant			XP_047303953.1
GP9	XM_005247374.4	c.*272_*276delTGTACinsGTGGG		downstream_gene_variant			XP_005247431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP9	ENST00000307395.5	c.70_74delTGTACinsGTGGG	p.CysThr24ValGly	missense_variant		1	NM_000174.5	ENSP00000303942.4

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

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

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;