rs11732666

Variant names:

• chr4-121902897-C-T
• rs11732666
• NM_001130698.2:c.2418G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-121902897-C-T
• chr4-121902897-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001130698.2(TRPC3):​c.2418G>A​(p.Arg806Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,612,158 control chromosomes in the GnomAD database, including 96,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6925 hom., cov: 32)
  • Exomes 𝑓: 0.35 (89942 hom.)
• Consequence: TRPC3 NM_001130698.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.635
• Publications: 20 publications found

Genes affected

TRPC3 (HGNC:12335): (transient receptor potential cation channel subfamily C member 3) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TRPC3 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 41

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 4-121902897-C-T is Benign according to our data. Variant chr4-121902897-C-T is described in ClinVar as Benign. ClinVar VariationId is 2135323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.635 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130698.2. 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
	TRPC3	NM_001130698.2	MANE Select	c.2418G>A	p.Arg806Arg	synonymous	Exon 9 of 12	NP_001124170.1	Q13507-2
	TRPC3	NM_001366479.2		c.2418G>A	p.Arg806Arg	synonymous	Exon 9 of 11	NP_001353408.1
	TRPC3	NM_003305.2		c.2199G>A	p.Arg733Arg	synonymous	Exon 8 of 11	NP_003296.1	Q13507-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC3	ENST00000379645.8	TSL:1 MANE Select	c.2418G>A	p.Arg806Arg	synonymous	Exon 9 of 12	ENSP00000368966.3	Q13507-2
	TRPC3	ENST00000264811.9	TSL:1	c.2199G>A	p.Arg733Arg	synonymous	Exon 8 of 11	ENSP00000264811.5	Q13507-3
	TRPC3	ENST00000513531.1	TSL:1	c.2034G>A	p.Arg678Arg	synonymous	Exon 7 of 10	ENSP00000426899.1	J3QTB0

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43436 AN: 151846 Hom.: 6920 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.343 AC: 85799 AN: 250284 AF XY: 0.341

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.413

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.347 AC: 506179 AN: 1460194 Hom.: 89942 Cov.: 36 AF XY: 0.345 AC XY: 250400 AN XY: 726356

African (AFR) AF: 0.122 AC: 4082 AN: 33438

American (AMR) AF: 0.442 AC: 19717 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7346 AN: 26098

East Asian (EAS) AF: 0.488 AC: 19297 AN: 39566

South Asian (SAS) AF: 0.325 AC: 27939 AN: 86096

European-Finnish (FIN) AF: 0.390 AC: 20787 AN: 53368

Middle Eastern (MID) AF: 0.333 AC: 1914 AN: 5754

European-Non Finnish (NFE) AF: 0.347 AC: 385151 AN: 1110982

Other (OTH) AF: 0.331 AC: 19946 AN: 60318

GnomAD4 genome AF: 0.286 AC: 43455 AN: 151964 Hom.: 6925 Cov.: 32 AF XY: 0.291 AC XY: 21629 AN XY: 74260

African (AFR) AF: 0.133 AC: 5505 AN: 41462

American (AMR) AF: 0.368 AC: 5611 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 993 AN: 3464

East Asian (EAS) AF: 0.427 AC: 2201 AN: 5158

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4816

European-Finnish (FIN) AF: 0.374 AC: 3945 AN: 10560

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22654 AN: 67938

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.316 Hom.: 10354

Bravo AF: 0.278

Asia WGS AF: 0.346 AC: 1204 AN: 3478

EpiCase AF: 0.319

EpiControl AF: 0.324

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		0.64
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11732666; hg19: chr4-122824052; COSMIC: COSV53373195;