10-66465837-T-C

Variant names:

• chr10-66465837-T-C
• rs2456664
• NM_013266.4:c.1531+54780A>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.1531+54780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,006 control chromosomes in the GnomAD database, including 3,574 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 0.15 (3574 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1531+54780A>G		intron_variant	Intron 11 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1531+54780A>G		intron_variant	Intron 11 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22761 AN: 151888 Hom.: 3566 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0386

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.150 AC: 22817 AN: 152006 Hom.: 3574 Cov.: 32 AF XY: 0.158 AC XY: 11774 AN XY: 74328

African (AFR) AF: 0.257 AC: 10661 AN: 41444

American (AMR) AF: 0.176 AC: 2679 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3464

East Asian (EAS) AF: 0.773 AC: 3960 AN: 5124

South Asian (SAS) AF: 0.299 AC: 1437 AN: 4814

European-Finnish (FIN) AF: 0.0712 AC: 756 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0386 AC: 2623 AN: 67976

Other (OTH) AF: 0.145 AC: 307 AN: 2112

Alfa AF: 0.0983 Hom.: 189

Bravo AF: 0.165

Asia WGS AF: 0.523 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		0.15
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: rs2456664; hg19: chr10-68225595;