rs6480140

Variant names:

• chr10-66109123-A-C
• rs6480140
• NM_013266.4:c.1885-5874T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-66109123-A-C
• chr10-66109123-A-G

Variant summary

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

The NM_013266.4(CTNNA3):​c.1885-5874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,030 control chromosomes in the GnomAD database, including 17,704 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 0.46 (17704 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• 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

ENSG00000273360 (HGNC:58344):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1885-5874T>G		intron_variant	Intron 13 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1885-5874T>G		intron_variant	Intron 13 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69583 AN: 151912 Hom.: 17675 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.458 AC: 69660 AN: 152030 Hom.: 17704 Cov.: 32 AF XY: 0.456 AC XY: 33882 AN XY: 74324

African (AFR) AF: 0.688 AC: 28534 AN: 41476

American (AMR) AF: 0.473 AC: 7211 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1754 AN: 5154

South Asian (SAS) AF: 0.380 AC: 1833 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3953 AN: 10560

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23741 AN: 67988

Other (OTH) AF: 0.433 AC: 913 AN: 2108

Alfa AF: 0.406 Hom.: 1783

Bravo AF: 0.479

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.71
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: rs6480140; hg19: chr10-67868881;