rs1344089

Positions:

• chr10-66874615-G-A
• chr10-66874615-G-C
• chr10-66874615-G-T

Variant summary

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

The NM_013266.4(CTNNA3):​c.1048-99091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,894 control chromosomes in the GnomAD database, including 14,310 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 0.43 (14310 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1048-99091C>T		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1048-99091C>T		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65205 AN: 151776 Hom.: 14299 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.430 AC: 65253 AN: 151894 Hom.: 14310 Cov.: 32 AF XY: 0.428 AC XY: 31733 AN XY: 74228

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.417

Alfa AF: 0.314 Hom.: 821

Bravo AF: 0.417

Asia WGS AF: 0.291 AC: 1006 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.72

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: rs1344089; hg19: chr10-68634373;