chr19-55027664-C-T

Position:

• chr19-55027664-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000310373.7(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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in UniProt as Likely_pathogenic (no stars).

• Frequency: Genomes: not found (cov: 35)
• Consequence: GP6 ENST00000310373.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-55027664-C-T is Pathogenic according to our data. Variant chr19-55027664-C-T is described in UniProt as null. Variant chr19-55027664-C-T is described in UniProt as null.
• BP4: Computational evidence support a benign effect (MetaRNN=0.137665). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2	c.524G>A	p.Ser175Asn	missense_variant	4/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3	n.122-15136C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.524G>A	p.Ser175Asn	missense_variant	4/8	1	NM_001083899.2	ENSP00000308782
GP6-AS1	ENST00000593060.5	n.156-15136C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;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;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.66	N;N;N;.
REVEL	Benign	0.069
Sift	Uncertain	0.0050	D;D;D;.
Sift4G	Benign	0.30	T;T;T;.
Polyphen		0.014	B;B;B;.
Vest4		0.39
MutPred		0.61		Loss of glycosylation at S175 (P = 0.0224);Loss of glycosylation at S175 (P = 0.0224);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

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

LitVar

Other links and lift over

dbSNP: rs387906919; hg19: chr19-55539032;