10-67242120-C-T

Variant names:

• chr10-67242120-C-T
• rs10997591
• NM_013266.4:c.580-22250G>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.580-22250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,050 control chromosomes in the GnomAD database, including 22,532 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 0.50 (22532 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.580-22250G>A		intron	N/A	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.580-22250G>A		intron	N/A	NP_001120856.1	Q9UI47-1
	CTNNA3	NM_001291133.2		c.616-22250G>A		intron	N/A	NP_001278062.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.580-22250G>A		intron	N/A	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.580-22250G>A		intron	N/A	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.580-22250G>A		intron	N/A	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75725 AN: 151932 Hom.: 22478 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.499 AC: 75838 AN: 152050 Hom.: 22532 Cov.: 32 AF XY: 0.494 AC XY: 36714 AN XY: 74316

African (AFR) AF: 0.846 AC: 35115 AN: 41502

American (AMR) AF: 0.368 AC: 5620 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2464 AN: 5164

South Asian (SAS) AF: 0.490 AC: 2366 AN: 4826

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10550

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24807 AN: 67962

Other (OTH) AF: 0.455 AC: 960 AN: 2108

Alfa AF: 0.352 Hom.: 2472

Bravo AF: 0.514

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.49
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: rs10997591; hg19: chr10-69001878;