chr19-55027664-C-T

Variant names:

• chr19-55027664-C-T
• rs387906919
• NM_016363.5:c.524G>A

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.524G>A​(p.Ser175Asn) 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.

• Frequency: Genomes: not found (cov: 35)
• Consequence: GP6 NM_016363.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928
• Publications: 4 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=0.137665).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.524G>A	p.Ser175Asn	missense	Exon 4 of 8	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.524G>A	p.Ser175Asn	missense	Exon 4 of 8	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.524G>A	p.Ser175Asn	missense	Exon 4 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.524G>A	p.Ser175Asn	missense	Exon 4 of 8	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000310373.7	TSL:1	c.524G>A	p.Ser175Asn	missense	Exon 4 of 8	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000333884.2	TSL:1	c.524G>A	p.Ser175Asn	missense	Exon 4 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.93
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.069
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.30	T
Polyphen		0.014	B
Vest4		0.39
MutPred		0.61		Loss of glycosylation at S175 (P = 0.0224)
MVP		0.44
MPC		0.16
ClinPred		0.16	T
GERP RS		2.9
Varity_R		0.62
gMVP		0.40
Mutation Taster		=5/95	disease causing

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: rs387906919; hg19: chr19-55539032;