NM_001080471.3:c.938A>G

Variant names:

• chr1-156908163-A-G
• rs767363444
• NM_001080471.3:c.938A>G

Variant summary

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

The NM_001080471.3(PEAR1):​c.938A>G​(p.Gln313Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,603,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (1 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.480
• Publications: 1 publications found

Genes affected

PEAR1 (HGNC:33631): (platelet endothelial aggregation receptor 1) PEAR1 is a platelet receptor that signals upon the formation of platelet-platelet contacts independent of platelet activation and secondary to platelet aggregation (Nanda et al., 2005 [PubMed 15851471]).[supplied by OMIM, Mar 2008]

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=0.21287909).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080471.3. 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
	PEAR1	NM_001080471.3	MANE Select	c.938A>G	p.Gln313Arg	missense	Exon 9 of 23	NP_001073940.1	Q5VY43
	PEAR1	NM_001353682.2		c.746A>G	p.Gln249Arg	missense	Exon 9 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.746A>G	p.Gln249Arg	missense	Exon 10 of 24	NP_001340612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.938A>G	p.Gln313Arg	missense	Exon 9 of 23	ENSP00000292357.7	Q5VY43
	PEAR1	ENST00000971373.1		c.965A>G	p.Gln322Arg	missense	Exon 11 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.938A>G	p.Gln313Arg	missense	Exon 10 of 24	ENSP00000344465.3	Q5VY43

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151962 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000592 AC: 14 AN: 236572 AF XY: 0.0000387

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000645

Gnomad OTH exome AF: 0.000513

GnomAD4 exome AF: 0.0000579 AC: 84 AN: 1451414 Hom.: 1 Cov.: 36 AF XY: 0.0000429 AC XY: 31 AN XY: 722098

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.000180 AC: 8 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 85764

European-Finnish (FIN) AF: 0.0000218 AC: 1 AN: 45938

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1110326

Other (OTH) AF: 0.000233 AC: 14 AN: 60148

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151962 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41334

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.0000663 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.48
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.083
Sift	Benign	0.21	T
Sift4G	Benign	0.61	T
Polyphen		0.91	P
Vest4		0.35
MutPred		0.24		Gain of phosphorylation at T318 (P = 0.172)
MVP		0.59
MPC		0.30
ClinPred		0.042	T
GERP RS		4.2
Varity_R		0.073
gMVP		0.63
Mutation Taster		=81/19	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: rs767363444; hg19: chr1-156877955; COSMIC: COSV52773451; COSMIC: COSV52773451;