rs10997691

chr10-67521827-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013266.4(CTNNA3):c.579+15T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,610,468 control chromosomes in the GnomAD database, including 17,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1614 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15573 hom.)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0890

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-67521827-A-C is Benign according to our data. Variant chr10-67521827-A-C is described in ClinVar as [Benign]. Clinvar id is 1248579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521827-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.579+15T>G		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.579+15T>G		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19898 AN: 152038 Hom.: 1610 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.165 AC: 41059 AN: 249198 Hom.: 4226 AF XY: 0.171 AC XY: 23062 AN XY: 134740

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.288

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.133 AC: 194289 AN: 1458312 Hom.: 15573 Cov.: 31 AF XY: 0.139 AC XY: 100555 AN XY: 725472

Gnomad4 AFR exome AF: 0.0831

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.131 AC: 19904 AN: 152156 Hom.: 1614 Cov.: 32 AF XY: 0.140 AC XY: 10424 AN XY: 74368

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.121

Alfa AF: 0.121 Hom.: 315

Bravo AF: 0.117

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

Arrhythmogenic right ventricular dysplasia 13 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Benign	0.89

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: rs10997691; hg19: chr10-69281585;