Genetic Variant GP6:p.Arg573Trp (chr19-55014228-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000310373.7(GP6):c.1717A>T(p.Arg573Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R573G) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GP6
ENST00000310373.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.833

Publications

21 publications found

Variant links:

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GP6 links:

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

GP6-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1856868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310373.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GP6	NM_016363.5	MANE Select	c.*693A>T		3_prime_UTR	Exon 8 of 8	NP_057447.5
GP6	NM_001083899.2		c.1717A>T	p.Arg573Trp	missense	Exon 8 of 8	NP_001077368.2
GP6	NM_001256017.2		c.*693A>T		3_prime_UTR	Exon 7 of 7	NP_001242946.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GP6	ENST00000310373.7	TSL:1	c.1717A>T	p.Arg573Trp	missense	Exon 8 of 8	ENSP00000308782.3
GP6	ENST00000417454.5	TSL:1 MANE Select	c.*693A>T		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1
GP6	ENST00000333884.2	TSL:1	c.*693A>T		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

682134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

366650

African (AFR)

AF:

0.00

AC:

AN:

19144

American (AMR)

AF:

0.00

AC:

AN:

39664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21056

East Asian (EAS)

AF:

0.00

AC:

AN:

35784

South Asian (SAS)

AF:

0.00

AC:

AN:

68574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4184

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

420518

Other (OTH)

AF:

0.00

AC:

AN:

35224

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0087

M_CAP

Benign

0.022

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.95

PhyloP100

-0.83

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.29

REVEL

Benign

0.084

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.019

Polyphen

0.98

Vest4

0.27

MutPred

0.55

Loss of disorder (P = 0.0071)

MVP

0.14

MPC

0.58

ClinPred

0.38

GERP RS

-0.47

gMVP

0.039

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over