rs59743346

Variant names:

• chr11-101453125-TAAG-T
• rs59743346
• NM_004621.6:c.2645-22_2645-20delCTT

Your query was ambiguous. Multiple possible variants found:

• chr11-101453125-TAAG-T
• chr11-101453125-TAAG-TAAGAAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004621.6(TRPC6):​c.2645-22_2645-20delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,609,060 control chromosomes in the GnomAD database, including 51,845 homozygotes. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.31 (9656 hom., cov: 0)
  • Exomes 𝑓: 0.23 (42189 hom.)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.640

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-101453125-TAAG-T is Benign according to our data. Variant chr11-101453125-TAAG-T is described in ClinVar as [Benign]. Clinvar id is 259461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.2645-22_2645-20delCTT		intron_variant	Intron 12 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.2645-22_2645-20delCTT		intron_variant	Intron 12 of 12	1	NM_004621.6	ENSP00000340913.3
TRPC6	ENST00000360497.4	c.2480-22_2480-20delCTT		intron_variant	Intron 11 of 11	1		ENSP00000353687.4
TRPC6	ENST00000348423.8	c.2297-22_2297-20delCTT		intron_variant	Intron 10 of 10	1		ENSP00000343672.4
TRPC6	ENST00000532133.5	c.2411-22_2411-20delCTT		intron_variant	Intron 11 of 11	5		ENSP00000435574.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47358 AN: 151728 Hom.: 9618 Cov.: 0

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.222 AC: 55406 AN: 250076 Hom.: 7824 AF XY: 0.222 AC XY: 30016 AN XY: 135224

Gnomad AFR exome AF: 0.594

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.0529

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.229 AC: 333812 AN: 1457214 Hom.: 42189 AF XY: 0.229 AC XY: 166351 AN XY: 725118

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.312 AC: 47451 AN: 151846 Hom.: 9656 Cov.: 0 AF XY: 0.304 AC XY: 22588 AN XY: 74188

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.308

Alfa AF: 0.272 Hom.: 1253

Bravo AF: 0.326

Asia WGS AF: 0.189 AC: 659 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Focal segmental glomerulosclerosis 2 Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 04, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs59743346; hg19: chr11-101323856;