rs17511

Variant names:

• chr10-66319747-G-A
• rs17511
• NM_013266.4:c.1733-39126C>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.1733-39126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,836 control chromosomes in the GnomAD database, including 25,748 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 0.57 (25748 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1733-39126C>T		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1733-39126C>T		intron	N/A	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1733-39126C>T		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1733-39126C>T		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1733-39126C>T		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87183 AN: 151720 Hom.: 25733 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.575 AC: 87232 AN: 151836 Hom.: 25748 Cov.: 32 AF XY: 0.572 AC XY: 42439 AN XY: 74198

African (AFR) AF: 0.458 AC: 18972 AN: 41386

American (AMR) AF: 0.620 AC: 9461 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3211 AN: 5168

South Asian (SAS) AF: 0.572 AC: 2759 AN: 4822

European-Finnish (FIN) AF: 0.566 AC: 5961 AN: 10530

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43128 AN: 67892

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.613 Hom.: 46352

Bravo AF: 0.577

Asia WGS AF: 0.570 AC: 1982 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.60
PhyloP100		-0.13
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: rs17511; hg19: chr10-68079505;