4-121879832-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001130698.2(TRPC3):c.2670A>G(p.Glu890=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,607,222 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (74 hom., cov: 32)
  • Exomes 𝑓: 0.030 (794 hom.)
• Consequence: TRPC3 NM_001130698.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 4-121879832-T-C is Benign according to our data. Variant chr4-121879832-T-C is described in ClinVar as [Benign]. Clinvar id is 2003811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3360/152260) while in subpopulation NFE AF= 0.0319 (2170/67998). AF 95% confidence interval is 0.0308. There are 74 homozygotes in gnomad4. There are 1672 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 3361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC3	NM_001130698.2	c.2670A>G	p.Glu890=	synonymous_variant	12/12	ENST00000379645.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC3	ENST00000379645.8	c.2670A>G	p.Glu890=	synonymous_variant	12/12	1	NM_001130698.2	P4
TRPC3	ENST00000264811.9	c.2451A>G	p.Glu817=	synonymous_variant	11/11	1		A2
TRPC3	ENST00000513531.1	c.2286A>G	p.Glu762=	synonymous_variant	10/10	1
TRPC3	ENST00000506449.1	c.*1678A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3361 AN: 152142 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0219 AC: 5320 AN: 242886 Hom.: 103 AF XY: 0.0217 AC XY: 2853 AN XY: 131376

Gnomad AFR exome AF: 0.00446

Gnomad AMR exome AF: 0.00375

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00507

Gnomad FIN exome AF: 0.0595

Gnomad NFE exome AF: 0.0317

Gnomad OTH exome AF: 0.0191

GnomAD4 exome AF: 0.0295 AC: 42945 AN: 1454962 Hom.: 794 Cov.: 30 AF XY: 0.0286 AC XY: 20664 AN XY: 723564

Gnomad4 AFR exome AF: 0.00426

Gnomad4 AMR exome AF: 0.00426

Gnomad4 ASJ exome AF: 0.00806

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00500

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0338

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0221 AC: 3360 AN: 152260 Hom.: 74 Cov.: 32 AF XY: 0.0225 AC XY: 1672 AN XY: 74462

Gnomad4 AFR AF: 0.00501

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0268 Hom.: 41

Bravo AF: 0.0172

Asia WGS AF: 0.00202 AC: 8 AN: 3476

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	4.5
Dann	Benign	0.55

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: rs41278087; hg19: chr4-122800987;