11-101583461-G-A

Position:

chr11-101583461-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,531,530 control chromosomes in the GnomAD database, including 8,033 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 524 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7509 hom. )

Consequence

TRPC6
NM_004621.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.11

Variant links:

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

TRPC6 links:

TRPC6 (HGNC:):

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017862916).

BP6

Variant 11-101583461-G-A is Benign according to our data. Variant chr11-101583461-G-A is described in ClinVar as [Benign]. Clinvar id is 259463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	1/13	ENST00000344327.8	NP_004612.2	Q9Y210-1
TRPC6	XM_047427510.1 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	1/11		XP_047283466.1
TRPC6	XM_017018221.3 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	1/11		XP_016873710.1	Q9Y210-2
TRPC6	XM_047427509.1 linkuse as main transcript	c.-89+471C>T		intron_variant			XP_047283465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	1/13	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10941

AN:

152198

Hom.:

525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.0910

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0601

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0879

GnomAD3 exomes

AF:

0.0822

AC:

11147

AN:

135616

Hom.:

581

AF XY:

0.0846

AC XY:

6229

AN XY:

73614

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.0894

Gnomad EAS exome

AF:

0.0899

Gnomad SAS exome

AF:

0.0741

Gnomad FIN exome

AF:

0.0615

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.101

AC:

139875

AN:

1379216

Hom.:

7509

Cov.:

AF XY:

0.101

AC XY:

68468

AN XY:

678714

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0891

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.0730

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0718

AC:

10936

AN:

152314

Hom.:

524

Cov.:

AF XY:

0.0693

AC XY:

5159

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.0910

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0602

Gnomad4 FIN

AF:

0.0545

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0865

Alfa

AF:

0.0906

Hom.:

166

Bravo

AF:

0.0702

TwinsUK

AF:

0.110

AC:

408

ALSPAC

AF:

0.111

AC:

427

ESP6500AA

AF:

0.0187

AC:

ESP6500EA

AF:

0.0860

AC:

680

ExAC

AF:

0.0428

AC:

4203

Asia WGS

AF:

0.0590

AC:

206

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 2019	- -

Focal segmental glomerulosclerosis 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 14, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

T;.;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.82

T;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.049

D;D;D;D

Sift4G

Benign

0.89

T;T;T;T

Polyphen

0.093

B;.;B;B

Vest4

0.25

MPC

0.30

ClinPred

0.013

GERP RS

4.6

Varity_R

0.077

gMVP

0.44

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