4-121902897-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001130698.2(TRPC3):c.2418G>A(p.Arg806=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC3	NM_001130698.2	c.2418G>A	p.Arg806=	synonymous_variant	9/12	ENST00000379645.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC3	ENST00000379645.8	c.2418G>A	p.Arg806=	synonymous_variant	9/12	1	NM_001130698.2	P4
TRPC3	ENST00000264811.9	c.2199G>A	p.Arg733=	synonymous_variant	8/11	1		A2
TRPC3	ENST00000513531.1	c.2034G>A	p.Arg678=	synonymous_variant	7/10	1
TRPC3	ENST00000506449.1	c.*1426G>A		3_prime_UTR_variant, NMD_transcript_variant	9/12	1

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

GnomAD3 exomes AF: 0.343 AC: 85799 AN: 250284 Hom.: 15513 AF XY: 0.341 AC XY: 46068 AN XY: 135274

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 SAS exome AF: 0.320

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

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.331

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.282

Alfa AF: 0.318 Hom.: 9378

Bravo AF: 0.278

Asia WGS AF: 0.346 AC: 1204 AN: 3478

EpiCase AF: 0.319

EpiControl AF: 0.324

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	10
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

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