rs12366144

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004621.6(TRPC6):c.1683T>C(p.Asn561Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,812 control chromosomes in the GnomAD database, including 53,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8742 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45006 hom. )

Consequence

TRPC6
NM_004621.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.17

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-101476362-A-G is Benign according to our data. Variant chr11-101476362-A-G is described in ClinVar as [Benign]. Clinvar id is 259455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.1683T>C	p.Asn561Asn	synonymous_variant	Exon 6 of 13	ENST00000344327.8	NP_004612.2	Q9Y210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPC6	ENST00000344327.8 link	c.1683T>C	p.Asn561Asn	synonymous_variant	Exon 6 of 13	1	NM_004621.6	ENSP00000340913.3	Q9Y210-1
TRPC6	ENST00000360497.4 link	c.1518T>C	p.Asn506Asn	synonymous_variant	Exon 5 of 12	1		ENSP00000353687.4	Q9Y210-3
TRPC6	ENST00000348423.8 link	c.1335T>C	p.Asn445Asn	synonymous_variant	Exon 4 of 11	1		ENSP00000343672.4	Q9Y210-2
TRPC6	ENST00000532133.5 link	c.1511-2589T>C		intron_variant	Intron 5 of 11	5		ENSP00000435574.1	E9PJN4

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46699

AN:

151942

Hom.:

8718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0586

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.228

AC:

57351

AN:

251284

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.545

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.0455

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.240

AC:

351065

AN:

1461752

Hom.:

45006

Cov.:

AF XY:

0.241

AC XY:

174894

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.555

AC:

18586

AN:

33474

American (AMR)

AF:

0.141

AC:

6311

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5975

AN:

26132

East Asian (EAS)

AF:

0.0971

AC:

3853

AN:

39696

South Asian (SAS)

AF:

0.257

AC:

22145

AN:

86252

European-Finnish (FIN)

AF:

0.201

AC:

10734

AN:

53414

Middle Eastern (MID)

AF:

0.333

AC:

1919

AN:

5764

European-Non Finnish (NFE)

AF:

0.239

AC:

266219

AN:

1111906

Other (OTH)

AF:

0.254

AC:

15323

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14847

29695

44542

59390

74237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.308

AC:

46775

AN:

152060

Hom.:

8742

Cov.:

AF XY:

0.301

AC XY:

22387

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.533

AC:

22086

AN:

41432

American (AMR)

AF:

0.198

AC:

3031

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

823

AN:

3472

East Asian (EAS)

AF:

0.0583

AC:

302

AN:

5180

South Asian (SAS)

AF:

0.244

AC:

1175

AN:

4818

European-Finnish (FIN)

AF:

0.197

AC:

2083

AN:

10588

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16373

AN:

67986

Other (OTH)

AF:

0.296

AC:

624

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1509

3017

4526

6034

7543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.271

Hom.:

2986

Bravo

AF:

0.314

Asia WGS

AF:

0.186

AC:

648

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.243

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 14, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 41. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.3

(source)

DANN

Benign

0.61

PhyloP100

1.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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rs12366144

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over