NM_016363.5:c.484A>G

Variant names:

• chr19-55027704-T-C
• rs892090
• NM_016363.5:c.484A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016363.5(GP6):​c.484A>G​(p.Arg162Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R162R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GP6 NM_016363.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 25 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]

ENSG00000267149 (HGNC:):

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

ACMG classification

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=0.16623735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.484A>G	p.Arg162Gly	missense	Exon 4 of 8	NP_057447.5
	GP6	NM_001083899.2		c.484A>G	p.Arg162Gly	missense	Exon 4 of 8	NP_001077368.2
	GP6	NM_001256017.2		c.484A>G	p.Arg162Gly	missense	Exon 4 of 7	NP_001242946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.484A>G	p.Arg162Gly	missense	Exon 4 of 8	ENSP00000394922.1
	GP6	ENST00000310373.7	TSL:1	c.484A>G	p.Arg162Gly	missense	Exon 4 of 8	ENSP00000308782.3
	GP6	ENST00000333884.2	TSL:1	c.484A>G	p.Arg162Gly	missense	Exon 4 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.87	L
PhyloP100		0.19
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.016
Sift	Benign	0.042	D
Sift4G	Benign	0.14	T
Polyphen		0.053	B
Vest4		0.20
MutPred		0.66		Loss of solvent accessibility (P = 0.0769)
MVP		0.17
MPC		0.24
ClinPred		0.10	T
GERP RS		0.57
Varity_R		0.34
gMVP		0.45
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs892090; hg19: chr19-55539072;