4-121902842-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001130698.2(TRPC3):c.2463+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,570,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: TRPC3 NM_001130698.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-121902842-C-T is Benign according to our data. Variant chr4-121902842-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2066242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 107 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC3	NM_001130698.2	c.2463+10G>A		intron_variant		ENST00000379645.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC3	ENST00000379645.8	c.2463+10G>A		intron_variant		1	NM_001130698.2	P4
TRPC3	ENST00000264811.9	c.2244+10G>A		intron_variant		1		A2
TRPC3	ENST00000513531.1	c.2079+10G>A		intron_variant		1
TRPC3	ENST00000506449.1	c.*1471+10G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000307 AC: 68 AN: 221794 Hom.: 0 AF XY: 0.000191 AC XY: 23 AN XY: 120326

Gnomad AFR exome AF: 0.00204

Gnomad AMR exome AF: 0.0000385

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000588

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000977

Gnomad NFE exome AF: 0.000296

Gnomad OTH exome AF: 0.000192

GnomAD4 exome AF: 0.000445 AC: 632 AN: 1418684 Hom.: 0 Cov.: 28 AF XY: 0.000404 AC XY: 284 AN XY: 703442

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000467

Gnomad4 OTH exome AF: 0.000803

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74442

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000937 Hom.: 0

Bravo AF: 0.000846

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 09, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.013
Dann	Benign	0.21

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

LitVar

Other links and lift over

dbSNP: rs199536092; hg19: chr4-122823997;