rs12774061

Positions:

• chr10-66731149-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013266.4(CTNNA3):​c.1281+35115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,048 control chromosomes in the GnomAD database, including 11,922 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 0.39 (11922 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1281+35115A>G		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1281+35115A>G		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59053 AN: 151930 Hom.: 11909 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.389 AC: 59105 AN: 152048 Hom.: 11922 Cov.: 32 AF XY: 0.390 AC XY: 28960 AN XY: 74312

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.386

Alfa AF: 0.405 Hom.: 1620

Bravo AF: 0.368

Asia WGS AF: 0.277 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.78

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: rs12774061; hg19: chr10-68490907;