NM_001080471.3:c.190A>G

Variant names:

• chr1-156904836-A-G
• rs139334858
• NM_001080471.3:c.190A>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.190A>G​(p.Thr64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600
• Publications: 0 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=0.08623785).

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.190A>G	p.Thr64Ala	missense	Exon 3 of 23	NP_001073940.1	Q5VY43
	PEAR1	NM_001353682.2		c.-149A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.-149A>G		5_prime_UTR_premature_start_codon_gain	Exon 4 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.190A>G	p.Thr64Ala	missense	Exon 3 of 23	ENSP00000292357.7	Q5VY43
	PEAR1	ENST00000971373.1		c.190A>G	p.Thr64Ala	missense	Exon 4 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.190A>G	p.Thr64Ala	missense	Exon 4 of 24	ENSP00000344465.3	Q5VY43

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151854 Hom.: 0 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: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250418 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461506 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727070

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111814

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151972 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67908

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.057
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	3.5
DANN	Benign	0.82
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.060
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.18
Sift	Benign	0.082	T
Sift4G	Benign	0.20	T
Polyphen		0.0020	B
Vest4		0.079
MVP		0.27
MPC		0.15
ClinPred		0.020	T
GERP RS		-7.4
Varity_R		0.058
gMVP		0.30
Mutation Taster		=91/9	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: rs139334858; hg19: chr1-156874628;