chr10-67244489-A-G

Variant names:

• chr10-67244489-A-G
• rs1904634
• NM_013266.4:c.580-24619T>C

Variant summary

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

The NM_013266.4(CTNNA3):​c.580-24619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,110 control chromosomes in the GnomAD database, including 7,574 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 0.24 (7574 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.580-24619T>C		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.580-24619T>C		intron_variant	Intron 5 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36782 AN: 151988 Hom.: 7545 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.242 AC: 36863 AN: 152110 Hom.: 7574 Cov.: 32 AF XY: 0.243 AC XY: 18067 AN XY: 74364

African (AFR) AF: 0.558 AC: 23112 AN: 41422

American (AMR) AF: 0.178 AC: 2714 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 323 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1766 AN: 5168

South Asian (SAS) AF: 0.192 AC: 925 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6209 AN: 68010

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.142 Hom.: 10224

Bravo AF: 0.262

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.30
PhyloP100		-2.0
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: rs1904634; hg19: chr10-69004247;