chr1-156904755-A-G

Variant names:

• chr1-156904755-A-G
• NM_001080471.3:c.109A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353682.2(PEAR1):​c.-230A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,812 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: 0.0000014 (0 hom.)
• Consequence: PEAR1 NM_001353682.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18554097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.109A>G	p.Thr37Ala	missense_variant	Exon 3 of 23	ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.109A>G	p.Thr37Ala	missense_variant	Exon 3 of 23	5	NM_001080471.3	ENSP00000292357.7
PEAR1	ENST00000338302.7	c.109A>G	p.Thr37Ala	missense_variant	Exon 4 of 24	5		ENSP00000344465.3
PEAR1	ENST00000455314.5	c.109A>G	p.Thr37Ala	missense_variant	Exon 3 of 6	2		ENSP00000389742.1
PEAR1	ENST00000444016.5	n.109A>G		non_coding_transcript_exon_variant	Exon 3 of 7	3		ENSP00000397870.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458812 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109A>G (p.T37A) alteration is located in exon 3 (coding exon 2) of the PEAR1 gene. This alteration results from a A to G substitution at nucleotide position 109, causing the threonine (T) at amino acid position 37 to be replaced by an alanine (A). 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	Benign	0.077
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.64	.;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.069	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.035	B;.;B
Vest4		0.28
MutPred		0.51		Loss of glycosylation at T37 (P = 0.0239);Loss of glycosylation at T37 (P = 0.0239);Loss of glycosylation at T37 (P = 0.0239);
MVP		0.75
MPC		0.15
ClinPred		0.46	T
GERP RS		3.6
Varity_R		0.069
gMVP		0.49

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: chr1-156874547;