3-129061554-C-T

Variant names:

• chr3-129061554-C-T
• rs886057960
• NM_000174.5:c.-78C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000174.5(GP9):​c.-78C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 496,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: GP9 NM_000174.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 0 publications found

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]

GP9 Gene-Disease associations (from GenCC):

• Bernard-Soulier syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000174.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP9	NM_000174.5	MANE Select	c.-78C>T		5_prime_UTR	Exon 2 of 3	NP_000165.1	P14770

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP9	ENST00000307395.5	TSL:1 MANE Select	c.-78C>T		5_prime_UTR	Exon 2 of 3	ENSP00000303942.4	P14770
	GP9	ENST00000900754.1		c.-74C>T		5_prime_UTR	Exon 2 of 3	ENSP00000570813.1
	GP9	ENST00000900756.1		c.-78C>T		5_prime_UTR	Exon 1 of 2	ENSP00000570815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000201 AC: 1 AN: 496638 Hom.: 0 Cov.: 5 AF XY: 0.00000380 AC XY: 1 AN XY: 263132

African (AFR) AF: 0.0000676 AC: 1 AN: 14790

American (AMR) AF: 0.00 AC: 0 AN: 29940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15782

East Asian (EAS) AF: 0.00 AC: 0 AN: 31578

South Asian (SAS) AF: 0.00 AC: 0 AN: 51938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 291776

Other (OTH) AF: 0.00 AC: 0 AN: 28038

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		-0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs886057960; hg19: chr3-128780397;