3-142806016-G-T

Variant names:

• chr3-142806016-G-T
• rs1132030
• NM_001251845.2:c.2163G>T

Variant summary

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

The NM_001251845.2(TRPC1):​c.2163G>T​(p.Arg721Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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: TRPC1 NM_001251845.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

Genes affected

TRPC1 (HGNC:12333): (transient receptor potential cation channel subfamily C member 1) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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=0.11896747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.2163G>T	p.Arg721Ser	missense_variant	Exon 13 of 13	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.2163G>T	p.Arg721Ser	missense_variant	Exon 13 of 13	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.2061G>T	p.Arg687Ser	missense_variant	Exon 12 of 12	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.2472G>T	p.Arg824Ser	missense_variant	Exon 13 of 13			ENSP00000513620.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.030	N;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.12	N;N;.
REVEL	Uncertain	0.31
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.71	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.29
MutPred		0.41		Gain of ubiquitination at K724 (P = 0.026);.;.;
MVP		0.28
MPC		1.1
ClinPred		0.36	T
GERP RS		3.0
Varity_R		0.18
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1132030; hg19: chr3-142524858;