chr10-66219101-G-A

Variant names:

• chr10-66219101-G-A
• rs10822753
• NM_013266.4:c.1884+61369C>T

Variant summary

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

The NM_013266.4(CTNNA3):​c.1884+61369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,996 control chromosomes in the GnomAD database, including 18,045 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 0.48 (18045 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 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.1884+61369C>T		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1884+61369C>T		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.1884+61369C>T		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1884+61369C>T		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1884+61369C>T		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72981 AN: 151878 Hom.: 18025 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.481 AC: 73052 AN: 151996 Hom.: 18045 Cov.: 31 AF XY: 0.484 AC XY: 35943 AN XY: 74292

African (AFR) AF: 0.374 AC: 15490 AN: 41436

American (AMR) AF: 0.451 AC: 6885 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3472

East Asian (EAS) AF: 0.502 AC: 2580 AN: 5144

South Asian (SAS) AF: 0.590 AC: 2847 AN: 4824

European-Finnish (FIN) AF: 0.507 AC: 5353 AN: 10552

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.532 AC: 36188 AN: 67980

Other (OTH) AF: 0.472 AC: 996 AN: 2112

Alfa AF: 0.507 Hom.: 26683

Bravo AF: 0.474

Asia WGS AF: 0.478 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		0.093
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: rs10822753; hg19: chr10-67978859;