Variant 3-142792828-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001251845.2(TRPC1):c.1442A>G(p.His481Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000287 in 1,428,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TRPC1
NM_001251845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17138767).

BS2

High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC1	NM_001251845.2 linkuse as main transcript	c.1442A>G	p.His481Arg	missense_variant	9/13	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.1442A>G	p.His481Arg	missense_variant	9/13	1	NM_001251845.2	ENSP00000419313	P1	P48995-1
TRPC1	ENST00000273482.10 linkuse as main transcript	c.1340A>G	p.His447Arg	missense_variant	8/12	1		ENSP00000273482		P48995-2
TRPC1	ENST00000698238.1 linkuse as main transcript	c.1751A>G	p.His584Arg	missense_variant	9/13			ENSP00000513620

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000312

AC:

AN:

224662

Hom.:

AF XY:

0.0000246

AC XY:

AN XY:

121916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000478

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1428978

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

710604

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000767

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:

0.0000328

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

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

Jan 26, 2022

The c.1340A>G (p.H447R) alteration is located in exon 8 (coding exon 8) of the TRPC1 gene. This alteration results from a A to G substitution at nucleotide position 1340, causing the histidine (H) at amino acid position 447 to be replaced by an arginine (R). 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

0.066

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Uncertain

0.47

T;.;.

Eigen

Benign

-0.093

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.090

N;.;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.19

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.45

T;T;.

Sift4G

Benign

0.85

T;T;T

Polyphen

0.042

B;B;B

Vest4

0.21

MutPred

0.58

Gain of MoRF binding (P = 0.0816);.;.;

MVP

0.71

MPC

1.3

ClinPred

0.11

GERP RS

5.2

Varity_R

0.17

gMVP

0.50

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