rs1029492268

Variant names:

• chr19-55014101-A-G
• rs1029492268
• ENST00000310373.7:c.1844T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001083899.2(GP6):​c.1844T>C​(p.Met615Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000076 in 671,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.330
• Publications: 0 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.07221693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083899.2. 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
	GP6	NM_016363.5	MANE Select	c.*820T>C		3_prime_UTR	Exon 8 of 8	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.1844T>C	p.Met615Thr	missense	Exon 8 of 8	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.*820T>C		3_prime_UTR	Exon 7 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000310373.7	TSL:1	c.1844T>C	p.Met615Thr	missense	Exon 8 of 8	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*820T>C		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000333884.2	TSL:1	c.*820T>C		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151970 Hom.: 1 Cov.: 33

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: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000773 AC: 1 AN: 129418 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000953

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000712 AC: 37 AN: 519322 Hom.: 0 Cov.: 0 AF XY: 0.0000603 AC XY: 17 AN XY: 281808

African (AFR) AF: 0.0000652 AC: 1 AN: 15328

American (AMR) AF: 0.0000297 AC: 1 AN: 33676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19252

East Asian (EAS) AF: 0.000102 AC: 3 AN: 29526

South Asian (SAS) AF: 0.00 AC: 0 AN: 61668

European-Finnish (FIN) AF: 0.0000336 AC: 1 AN: 29776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3922

European-Non Finnish (NFE) AF: 0.0000874 AC: 26 AN: 297454

Other (OTH) AF: 0.000174 AC: 5 AN: 28720

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 151970 Hom.: 1 Cov.: 33 AF XY: 0.0000943 AC XY: 7 AN XY: 74230

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000756 Hom.: 1

Bravo AF: 0.0000416

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.42
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.33
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Polyphen		0.092	B
Vest4		0.31
MutPred		0.32		Loss of sheet (P = 0.0817)
MVP		0.088
MPC		0.22
ClinPred		0.13	T
GERP RS		0.23
gMVP		0.030
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1029492268; hg19: chr19-55525469;