chr1-156912965-C-T

Variant names:

• chr1-156912965-C-T
• rs41299597
• NM_001080471.3:c.2405C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080471.3(PEAR1):​c.2405C>T​(p.Ser802Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	NM_001080471.3	MANE Select	c.2405C>T	p.Ser802Phe	missense	Exon 18 of 23	NP_001073940.1
	PEAR1	NM_001353682.2		c.2213C>T	p.Ser738Phe	missense	Exon 18 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.2213C>T	p.Ser738Phe	missense	Exon 19 of 24	NP_001340612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.2405C>T	p.Ser802Phe	missense	Exon 18 of 23	ENSP00000292357.7
	PEAR1	ENST00000338302.7	TSL:5	c.2405C>T	p.Ser802Phe	missense	Exon 19 of 24	ENSP00000344465.3
	PEAR1	ENST00000469390.5	TSL:2	n.2133C>T		non_coding_transcript_exon	Exon 13 of 18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.7	L
PhyloP100		5.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.77
MutPred		0.39		Loss of disorder (P = 8e-04)
MVP		0.76
MPC		0.50
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.33
gMVP		0.47
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41299597; hg19: chr1-156882757;