10-66001962-T-C

Variant names:

• chr10-66001962-T-C
• rs12356475
• NM_013266.4:c.2160-13165A>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.2160-13165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,024 control chromosomes in the GnomAD database, including 2,167 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 (2167 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.2160-13165A>G		intron_variant	Intron 15 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.2160-13165A>G		intron_variant	Intron 15 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22929 AN: 151902 Hom.: 2163 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.151 AC: 22938 AN: 152024 Hom.: 2167 Cov.: 32 AF XY: 0.160 AC XY: 11883 AN XY: 74300

African (AFR) AF: 0.0567 AC: 2353 AN: 41528

American (AMR) AF: 0.232 AC: 3535 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1072 AN: 5158

South Asian (SAS) AF: 0.280 AC: 1348 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2754 AN: 10544

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10833 AN: 67952

Other (OTH) AF: 0.154 AC: 324 AN: 2106

Alfa AF: 0.153 Hom.: 404

Bravo AF: 0.145

Asia WGS AF: 0.260 AC: 903 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		1.3
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: rs12356475; hg19: chr10-67761720;