NM_013266.4:c.1047+25435T>C

Variant names:

• chr10-67154882-A-G
• rs10822988
• NM_013266.4:c.1047+25435T>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.1047+25435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,974 control chromosomes in the GnomAD database, including 31,636 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 0.63 (31636 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815
• Publications: 0 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 (AFR) allele frequency at 95% confidence interval = 0.81 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.1047+25435T>C		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1047+25435T>C		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.1047+25435T>C		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1047+25435T>C		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1047+25435T>C		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96129 AN: 151856 Hom.: 31609 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.633 AC: 96209 AN: 151974 Hom.: 31636 Cov.: 31 AF XY: 0.637 AC XY: 47301 AN XY: 74288

African (AFR) AF: 0.817 AC: 33891 AN: 41462

American (AMR) AF: 0.560 AC: 8561 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2383 AN: 3464

East Asian (EAS) AF: 0.414 AC: 2121 AN: 5124

South Asian (SAS) AF: 0.623 AC: 3005 AN: 4822

European-Finnish (FIN) AF: 0.653 AC: 6899 AN: 10564

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37240 AN: 67944

Other (OTH) AF: 0.640 AC: 1354 AN: 2114

Alfa AF: 0.659 Hom.: 12759

Bravo AF: 0.636

Asia WGS AF: 0.540 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.81
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: rs10822988; hg19: chr10-68914640;