Genetic Variant GP6:p.Phe606Ile (chr19-55014129-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000310373.7(GP6):c.1816T>A(p.Phe606Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. F606L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 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: -1.84

Publications

22 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047500014).

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.*792T>A		3_prime_UTR	Exon 8 of 8	NP_057447.5
GP6	NM_001083899.2		c.1816T>A	p.Phe606Ile	missense	Exon 8 of 8	NP_001077368.2
GP6	NM_001256017.2		c.*792T>A		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.1816T>A	p.Phe606Ile	missense	Exon 8 of 8	ENSP00000308782.3
GP6	ENST00000417454.5	TSL:1 MANE Select	c.*792T>A		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1
GP6	ENST00000333884.2	TSL:1	c.*792T>A		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151972

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

539328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

292226

African (AFR)

AF:

0.00

AC:

AN:

15644

American (AMR)

AF:

0.00

AC:

AN:

34362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19778

East Asian (EAS)

AF:

0.00

AC:

AN:

31304

South Asian (SAS)

AF:

0.00

AC:

AN:

61880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4006

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

310260

Other (OTH)

AF:

0.00

AC:

AN:

29984

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74204

African (AFR)

AF:

0.00

AC:

AN:

41338

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.86

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0051

M_CAP

Benign

0.015

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

PhyloP100

-1.8

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.010

REVEL

Benign

0.0080

Sift

Uncertain

0.0050

Polyphen

0.010

Vest4

0.14

MutPred

0.22

Gain of sheet (P = 0.0827)

MVP

0.030

MPC

0.23

ClinPred

0.067

GERP RS

-0.47

gMVP

0.022

Mutation Taster

=99/1

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