rs10822753

Positions:

• chr10-66219101-G-A
• chr10-66219101-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1884+61369C>T		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1884+61369C>T		intron_variant		1	NM_013266.4	ENSP00000389714	P1

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

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.472

Alfa AF: 0.512 Hom.: 20947

Bravo AF: 0.474

Asia WGS AF: 0.478 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.78

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: rs10822753; hg19: chr10-67978859;