1-156908334-G-A

Variant summary

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

The NM_001080471.3(PEAR1):c.1109G>A(p.Ser370Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30414677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEAR1	NM_001080471.3	c.1109G>A	p.Ser370Asn	missense_variant	9/23	ENST00000292357.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEAR1	ENST00000292357.8	c.1109G>A	p.Ser370Asn	missense_variant	9/23	5	NM_001080471.3	P1
PEAR1	ENST00000338302.7	c.1109G>A	p.Ser370Asn	missense_variant	10/24	5		P1
PEAR1	ENST00000469390.5	n.837G>A		non_coding_transcript_exon_variant	4/18	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376852 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 677598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

The c.1109G>A (p.S370N) alteration is located in exon 9 (coding exon 8) of the PEAR1 gene. This alteration results from a G to A substitution at nucleotide position 1109, causing the serine (S) at amino acid position 370 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0056	T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N;N
MutationTaster	Benign	0.54	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.078
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.98	D;D
Vest4		0.34
MutPred		0.27		Loss of glycosylation at S370 (P = 0.0364);Loss of glycosylation at S370 (P = 0.0364);
MVP		0.43
MPC		0.55
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156878126; COSMIC: COSV52773568; COSMIC: COSV52773568;