Variant X-111776536-T-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 ENST00000262839.3(TRPC5):c.2699A>C(p.Asn900Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000909 in 1,209,748 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 3 hem. )

Consequence

TRPC5
ENST00000262839.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

Variant links:

Genes affected

TRPC5 (HGNC:12337): (transient receptor potential cation channel subfamily C member 5) This gene belongs to the transient receptor family. It encodes one of the seven mammalian TRPC (transient receptor potential channel) proteins. The encoded protein is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na(+)-H+ exchange regulatory factor (NHERF ), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1). [provided by RefSeq, May 2010]

TRPC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11861619).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC5	NM_012471.3 linkuse as main transcript	c.2699A>C	p.Asn900Thr	missense_variant	11/11	ENST00000262839.3	NP_036603.1
TRPC5	XM_017029774.2 linkuse as main transcript	c.2699A>C	p.Asn900Thr	missense_variant	12/12		XP_016885263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC5	ENST00000262839.3 linkuse as main transcript	c.2699A>C	p.Asn900Thr	missense_variant	11/11	1	NM_012471.3	ENSP00000262839	P1

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

111900

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34070

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000846

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

182155

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

66933

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000159

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097795

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363199

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0000555

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000357

AC:

AN:

111953

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34133

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000849

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Nov 21, 2023

The c.2699A>C (p.N900T) alteration is located in exon 11 (coding exon 10) of the TRPC5 gene. This alteration results from a A to C substitution at nucleotide position 2699, causing the asparagine (N) at amino acid position 900 to be replaced by a threonine (T). 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

0.092

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Uncertain

0.012

Sift4G

Benign

0.23

Polyphen

0.76

Vest4

0.20

MutPred

0.27

Gain of sheet (P = 0.0477);

MVP

0.57

MPC

0.19

ClinPred

0.10

GERP RS

5.6

Varity_R

0.23

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