rs10491057

Variant names:

• chr10-66885462-G-A
• rs10491057
• NM_013266.4:c.1048-109938C>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.1048-109938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,028 control chromosomes in the GnomAD database, including 180 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 0.025 (180 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 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.1048-109938C>T		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1048-109938C>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.1048-109938C>T		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1048-109938C>T		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1048-109938C>T		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3823 AN: 151910 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.00549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0252 AC: 3828 AN: 152028 Hom.: 180 Cov.: 32 AF XY: 0.0282 AC XY: 2092 AN XY: 74302

African (AFR) AF: 0.00547 AC: 227 AN: 41486

American (AMR) AF: 0.0455 AC: 694 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5156

South Asian (SAS) AF: 0.0845 AC: 406 AN: 4804

European-Finnish (FIN) AF: 0.0175 AC: 185 AN: 10558

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0152 AC: 1034 AN: 67990

Other (OTH) AF: 0.0304 AC: 64 AN: 2106

Alfa AF: 0.0239 Hom.: 106

Bravo AF: 0.0286

Asia WGS AF: 0.159 AC: 552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.071
DANN	Benign	0.46
PhyloP100		-1.8
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: rs10491057; hg19: chr10-68645220;