rs2456737

chr10-66395576-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):c.1532-16224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,900 control chromosomes in the GnomAD database, including 3,971 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 0.20 (3971 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1532-16224T>C		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1532-16224T>C		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31044 AN: 151782 Hom.: 3961 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.205 AC: 31076 AN: 151900 Hom.: 3971 Cov.: 31 AF XY: 0.199 AC XY: 14809 AN XY: 74264

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0994

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.205

Alfa AF: 0.160 Hom.: 1162

Bravo AF: 0.210

Asia WGS AF: 0.163 AC: 570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.41
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs2456737; hg19: chr10-68155334;