Variant chr3-142777645-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001251845.2(TRPC1):c.646A>G(p.Ile216Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,812 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRPC1
NM_001251845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.80

Variant links:

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]

TRPC1 links:

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ACMG classification

Classification made for transcript

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=0.39004192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC1	NM_001251845.2 linkuse as main transcript	c.646A>G	p.Ile216Val	missense_variant	5/13	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6 linkuse as main transcript	c.646A>G	p.Ile216Val	missense_variant	5/13	1	NM_001251845.2	ENSP00000419313	P1	P48995-1
TRPC1	ENST00000273482.10 linkuse as main transcript	c.544A>G	p.Ile182Val	missense_variant	4/12	1		ENSP00000273482		P48995-2
TRPC1	ENST00000698238.1 linkuse as main transcript	c.955A>G	p.Ile319Val	missense_variant	5/13			ENSP00000513620
TRPC1	ENST00000460401.1 linkuse as main transcript	c.*188A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000418708

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720254

show subpopulations

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.544A>G (p.I182V) alteration is located in exon 4 (coding exon 4) of the TRPC1 gene. This alteration results from a A to G substitution at nucleotide position 544, causing the isoleucine (I) at amino acid position 182 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.070

N;N;.

REVEL

Uncertain

0.41

Sift

Benign

0.48

T;T;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.90

P;B;B

Vest4

0.35

MutPred

0.57

Loss of catalytic residue at I216 (P = 0.0317);.;.;

MVP

0.70

MPC

1.9

ClinPred

0.93

GERP RS

5.5

Varity_R

0.12

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over