NM_013266.4:c.2160-34187C>T

Variant names:

• chr10-66022984-G-A
• rs7074141
• NM_013266.4:c.2160-34187C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.2160-34187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,024 control chromosomes in the GnomAD database, including 3,492 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 0.20 (3492 hom., cov: 33)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 3 publications found

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]

CTNNA3 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.2160-34187C>T		intron_variant	Intron 15 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.2160-34187C>T		intron_variant	Intron 15 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30703 AN: 151906 Hom.: 3485 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.202 AC: 30727 AN: 152024 Hom.: 3492 Cov.: 33 AF XY: 0.209 AC XY: 15506 AN XY: 74312

African (AFR) AF: 0.166 AC: 6864 AN: 41454

American (AMR) AF: 0.172 AC: 2627 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2630 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1852 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2201 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13054 AN: 67962

Other (OTH) AF: 0.193 AC: 409 AN: 2114

Alfa AF: 0.188 Hom.: 4828

Bravo AF: 0.196

Asia WGS AF: 0.440 AC: 1526 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.23
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7074141; hg19: chr10-67782742;