rs4746675

Positions:

• chr10-67192300-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.844-11780G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,364 control chromosomes in the GnomAD database, including 14,398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (14398 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

Genes affected

CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.844-11780G>T		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.844-11780G>T		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55121 AN: 151248 Hom.: 14355 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55214 AN: 151364 Hom.: 14398 Cov.: 32 AF XY: 0.365 AC XY: 27009 AN XY: 73990

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.324

Alfa AF: 0.276 Hom.: 1601

Bravo AF: 0.378

Asia WGS AF: 0.264 AC: 917 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.43

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: rs4746675; hg19: chr10-68952058;