rs16924415

Variant names:

• chr10-67354630-G-A
• rs16924415
• NM_013266.4:c.580-134760C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013266.4(CTNNA3):​c.580-134760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 151,958 control chromosomes in the GnomAD database, including 286 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 0.035 (286 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.580-134760C>T		intron_variant	Intron 5 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.580-134760C>T		intron_variant	Intron 5 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5279 AN: 151840 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0349 AC: 5304 AN: 151958 Hom.: 286 Cov.: 32 AF XY: 0.0375 AC XY: 2784 AN XY: 74258

African (AFR) AF: 0.0618 AC: 2563 AN: 41482

American (AMR) AF: 0.0480 AC: 731 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1222 AN: 5156

South Asian (SAS) AF: 0.126 AC: 606 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00133 AC: 90 AN: 67900

Other (OTH) AF: 0.0355 AC: 75 AN: 2110

Alfa AF: 0.0264 Hom.: 30

Bravo AF: 0.0400

Asia WGS AF: 0.163 AC: 565 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.66
PhyloP100		1.4
Mutation Taster		=99/1	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: rs16924415; hg19: chr10-69114388;