rs10997034

chr10-66280482-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013266.4(CTNNA3):c.1872C>A(p.Val624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,603,824 control chromosomes in the GnomAD database, including 1,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (305 hom., cov: 32)
  • Exomes 𝑓: 0.024 (927 hom.)
• Consequence: CTNNA3 NM_013266.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.29

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-66280482-G-T is Benign according to our data. Variant chr10-66280482-G-T is described in ClinVar as [Benign]. Clinvar id is 415368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-66280482-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1872C>A	p.Val624=	synonymous_variant	13/18	ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1872C>A	p.Val624=	synonymous_variant	13/18	1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7142 AN: 151926 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.0342 AC: 8270 AN: 241960 Hom.: 312 AF XY: 0.0355 AC XY: 4650 AN XY: 131068

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0665

Gnomad EAS exome AF: 0.0489

Gnomad SAS exome AF: 0.0841

Gnomad FIN exome AF: 0.00652

Gnomad NFE exome AF: 0.0182

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.0240 AC: 34798 AN: 1451780 Hom.: 927 Cov.: 30 AF XY: 0.0256 AC XY: 18516 AN XY: 722244

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.0553

Gnomad4 SAS exome AF: 0.0814

Gnomad4 FIN exome AF: 0.00700

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0356

GnomAD4 genome AF: 0.0471 AC: 7162 AN: 152044 Hom.: 305 Cov.: 32 AF XY: 0.0467 AC XY: 3468 AN XY: 74318

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.0577

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0404

Alfa AF: 0.0269 Hom.: 131

Bravo AF: 0.0488

Asia WGS AF: 0.0960 AC: 333 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Arrhythmogenic right ventricular dysplasia 13 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	7.4
Dann	Benign	0.75

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: rs10997034; hg19: chr10-68040240;