Variant 3-129061906-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_000174.5(GP9):c.167T>C(p.Leu56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GP9
NM_000174.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.85

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]

GP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a chain Platelet glycoprotein IX (size 160) in uniprot entity GPIX_HUMAN there are 33 pathogenic changes around while only 1 benign (97%) in NM_000174.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

PP5

Variant 3-129061906-T-C is Pathogenic according to our data. Variant chr3-129061906-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 13532.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-129061906-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GP9	NM_000174.5 linkuse as main transcript	c.167T>C	p.Leu56Pro	missense_variant	3/3	ENST00000307395.5
GP9	XM_047447997.1 linkuse as main transcript	c.167T>C	p.Leu56Pro	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP9	ENST00000307395.5 linkuse as main transcript	c.167T>C	p.Leu56Pro	missense_variant	3/3	1	NM_000174.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

248128

Hom.:

AF XY:

0.0000892

AC XY:

AN XY:

134560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000792

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000602

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000297

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bernard-Soulier syndrome type C

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

4.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.88

MutPred

0.86

Gain of disorder (P = 0.0132);

MVP

0.99

MPC

0.89

ClinPred

0.91

GERP RS

4.2

Varity_R

1.0

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over