rs4378283

Variant names:

• chr10-66375051-G-A
• rs4378283
• NM_013266.4:c.1732+4101C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-66375051-G-A
• chr10-66375051-G-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.1732+4101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,022 control chromosomes in the GnomAD database, including 845 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 0.082 (845 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1732+4101C>T		intron_variant	Intron 12 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1732+4101C>T		intron_variant	Intron 12 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12355 AN: 151904 Hom.: 836 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0815 AC: 12395 AN: 152022 Hom.: 845 Cov.: 31 AF XY: 0.0857 AC XY: 6368 AN XY: 74308

African (AFR) AF: 0.157 AC: 6518 AN: 41466

American (AMR) AF: 0.116 AC: 1762 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1157 AN: 5142

South Asian (SAS) AF: 0.0953 AC: 458 AN: 4808

European-Finnish (FIN) AF: 0.0826 AC: 873 AN: 10574

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0215 AC: 1461 AN: 67992

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0452 Hom.: 186

Bravo AF: 0.0876

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.59
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: rs4378283; hg19: chr10-68134809;