rs3802829

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15A) has been classified as Uncertain significance.

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

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004621.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	NM_004621.6	MANE Select	c.43C>T	p.Pro15Ser	missense	Exon 1 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.43C>T	p.Pro15Ser	missense	Exon 1 of 11	NP_001426264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.43C>T	p.Pro15Ser	missense	Exon 1 of 13	ENSP00000340913.3	Q9Y210-1
TRPC6	ENST00000360497.4	TSL:1	c.43C>T	p.Pro15Ser	missense	Exon 1 of 12	ENSP00000353687.4	Q9Y210-3
TRPC6	ENST00000348423.8	TSL:1	c.43C>T	p.Pro15Ser	missense	Exon 1 of 11	ENSP00000343672.4	Q9Y210-2

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

GnomAD2 exomes

AF:

0.0822

AC:

11147

AN:

135616

AF XY:

0.0846

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 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

African (AFR)

AF:

0.0163

AC:

490

AN:

30100

American (AMR)

AF:

0.0601

AC:

2123

AN:

35346

Ashkenazi Jewish (ASJ)

AF:

0.0891

AC:

2195

AN:

24648

East Asian (EAS)

AF:

0.128

AC:

4476

AN:

34848

South Asian (SAS)

AF:

0.0730

AC:

5706

AN:

78114

European-Finnish (FIN)

AF:

0.0638

AC:

2805

AN:

43996

Middle Eastern (MID)

AF:

0.0921

AC:

495

AN:

5376

European-Non Finnish (NFE)

AF:

0.108

AC:

115753

AN:

1069674

Other (OTH)

AF:

0.102

AC:

5832

AN:

57114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

7600

15200

22799

30399

37999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4310

8620

12930

17240

21550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0718

AC:

10936

AN:

152314

Hom.:

524

Cov.:

AF XY:

0.0693

AC XY:

5159

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41588

American (AMR)

AF:

0.0748

AC:

1145

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0910

AC:

316

AN:

3472

East Asian (EAS)

AF:

0.105

AC:

544

AN:

5158

South Asian (SAS)

AF:

0.0602

AC:

291

AN:

4834

European-Finnish (FIN)

AF:

0.0545

AC:

579

AN:

10620

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7076

AN:

68018

Other (OTH)

AF:

0.0865

AC:

183

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

560

1121

1681

2242

2802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0894

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Focal segmental glomerulosclerosis 2 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.24

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.80

REVEL

Uncertain

0.33

Sift

Benign

0.049

Sift4G

Benign

0.89

Polyphen

0.093

Vest4

0.25

MPC

0.30

ClinPred

0.013

GERP RS

4.6

PromoterAI

0.053

Neutral

(source)

Varity_R

0.077

gMVP

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over