rs997225

Variant names:

• chr10-66523212-C-T
• rs997225
• NM_013266.4:c.1375-2439G>A

Variant summary

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

The NM_013266.4(CTNNA3):​c.1375-2439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,048 control chromosomes in the GnomAD database, including 5,375 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 (5375 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 8 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

ENSG00000298814 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1375-2439G>A		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1375-2439G>A		intron	N/A	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1375-2439G>A		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1375-2439G>A		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1375-2439G>A		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36289 AN: 151930 Hom.: 5370 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.239 AC: 36329 AN: 152048 Hom.: 5375 Cov.: 32 AF XY: 0.247 AC XY: 18327 AN XY: 74318

African (AFR) AF: 0.172 AC: 7131 AN: 41480

American (AMR) AF: 0.267 AC: 4085 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4080 AN: 5164

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4826

European-Finnish (FIN) AF: 0.276 AC: 2912 AN: 10556

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15439 AN: 67976

Other (OTH) AF: 0.242 AC: 510 AN: 2104

Alfa AF: 0.234 Hom.: 20605

Bravo AF: 0.236

Asia WGS AF: 0.493 AC: 1711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.57
PhyloP100		0.51
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: rs997225; hg19: chr10-68282970;