Variant rs41278087 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001130698.2(TRPC3):c.2670A>G(p.Glu890=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,607,222 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 74 hom., cov: 32)

Exomes 𝑓: 0.030 ( 794 hom. )

Consequence

TRPC3
NM_001130698.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 4-121879832-T-C is Benign according to our data. Variant chr4-121879832-T-C is described in ClinVar as [Benign]. Clinvar id is 2003811.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3360/152260) while in subpopulation NFE AF= 0.0319 (2170/67998). AF 95% confidence interval is 0.0308. There are 74 homozygotes in gnomad4. There are 1672 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC3	NM_001130698.2 linkuse as main transcript	c.2670A>G	p.Glu890=	synonymous_variant	12/12	ENST00000379645.8	NP_001124170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC3	ENST00000379645.8 linkuse as main transcript	c.2670A>G	p.Glu890=	synonymous_variant	12/12	1	NM_001130698.2	ENSP00000368966	P4	Q13507-2
TRPC3	ENST00000264811.9 linkuse as main transcript	c.2451A>G	p.Glu817=	synonymous_variant	11/11	1		ENSP00000264811	A2	Q13507-3
TRPC3	ENST00000513531.1 linkuse as main transcript	c.2286A>G	p.Glu762=	synonymous_variant	10/10	1		ENSP00000426899
TRPC3	ENST00000506449.1 linkuse as main transcript	c.*1678A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	1		ENSP00000423866

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3361

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0219

AC:

5320

AN:

242886

Hom.:

103

AF XY:

0.0217

AC XY:

2853

AN XY:

131376

show subpopulations

Gnomad AFR exome

AF:

0.00446

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00507

Gnomad FIN exome

AF:

0.0595

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0191

GnomAD4 exome

AF:

0.0295

AC:

42945

AN:

1454962

Hom.:

794

Cov.:

AF XY:

0.0286

AC XY:

20664

AN XY:

723564

show subpopulations

Gnomad4 AFR exome

AF:

0.00426

Gnomad4 AMR exome

AF:

0.00426

Gnomad4 ASJ exome

AF:

0.00806

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00500

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0221

AC:

3360

AN:

152260

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

1672

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00501

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00202

AC:

AN:

3476

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.5

DANN

Benign

0.55

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