10-66328750-C-G

Variant names:

• chr10-66328750-C-G
• rs10762058
• NM_013266.4:c.1733-48129G>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.1733-48129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 149,990 control chromosomes in the GnomAD database, including 48,110 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 0.80 (48110 hom., cov: 25)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 22 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1733-48129G>C		intron_variant	Intron 12 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1733-48129G>C		intron_variant	Intron 12 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 119703 AN: 149874 Hom.: 48086 Cov.: 25

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.799 AC: 119775 AN: 149990 Hom.: 48110 Cov.: 25 AF XY: 0.794 AC XY: 58024 AN XY: 73122

African (AFR) AF: 0.754 AC: 30837 AN: 40922

American (AMR) AF: 0.774 AC: 11617 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2881 AN: 3446

East Asian (EAS) AF: 0.767 AC: 3854 AN: 5022

South Asian (SAS) AF: 0.809 AC: 3821 AN: 4724

European-Finnish (FIN) AF: 0.742 AC: 7570 AN: 10204

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 56542 AN: 67402

Other (OTH) AF: 0.783 AC: 1609 AN: 2056

Alfa AF: 0.831 Hom.: 28712

Bravo AF: 0.801

Asia WGS AF: 0.802 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.31
PhyloP100		0.0040
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: rs10762058; hg19: chr10-68088508;