Variant 4-121879816-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001130698.2(TRPC3):c.2686A>G(p.Ser896Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00174 in 1,608,510 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 82 hom. )

Consequence

TRPC3
NM_001130698.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

TRPC3 (HGNC:12335): (transient receptor potential cation channel subfamily C member 3) 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]

TRPC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TRPC3. . Gene score misZ 3.8433 (greater than the threshold 3.09). Trascript score misZ 3.0976 (greater than threshold 3.09). GenCC has associacion of gene with spinocerebellar ataxia type 41.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073967576).

BP6

Variant 4-121879816-T-C is Benign according to our data. Variant chr4-121879816-T-C is described in ClinVar as [Benign]. Clinvar id is 779331.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00226 (344/152320) while in subpopulation AMR AF= 0.0199 (304/15302). AF 95% confidence interval is 0.018. There are 11 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC3	NM_001130698.2 linkuse as main transcript	c.2686A>G	p.Ser896Gly	missense_variant	12/12	ENST00000379645.8	NP_001124170.1	Q13507-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC3	ENST00000379645.8 linkuse as main transcript	c.2686A>G	p.Ser896Gly	missense_variant	12/12	1	NM_001130698.2	ENSP00000368966.3		Q13507-2

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

346

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00780

AC:

1909

AN:

244622

Hom.:

AF XY:

0.00615

AC XY:

814

AN XY:

132310

show subpopulations

Gnomad AFR exome

AF:

0.000502

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.000799

Gnomad EAS exome

AF:

0.000280

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000986

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00168

AC:

2451

AN:

1456190

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1049

AN XY:

724158

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0517

Gnomad4 ASJ exome

AF:

0.000997

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000784

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152320

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

197

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000599

Hom.:

Bravo

AF:

0.00549

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00600

AC:

729

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-0.59

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.12

T;T;T

Vest4

0.39

MVP

0.75

MPC

0.84

ClinPred

0.039

GERP RS

4.9

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