rs10997691

Variant names:

• chr10-67521827-A-C
• rs10997691
• NM_013266.4:c.579+15T>G

Variant summary

Our verdict is Benign. The variant received -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:6
• Conservation: PhyloP100: 0.0890
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1248579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.579+15T>G		intron	N/A	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.579+15T>G		intron	N/A	NP_001120856.1	Q9UI47-1
	CTNNA3	NM_001291133.2		c.615+15T>G		intron	N/A	NP_001278062.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.579+15T>G		intron	N/A	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.579+15T>G		intron	N/A	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.579+15T>G		intron	N/A	ENSP00000508371.1	Q9UI47-1

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

GnomAD2 exomes AF: 0.165 AC: 41059 AN: 249198 AF XY: 0.171

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 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

African (AFR) AF: 0.0831 AC: 2766 AN: 33302

American (AMR) AF: 0.169 AC: 7438 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.0996 AC: 2583 AN: 25924

East Asian (EAS) AF: 0.307 AC: 12184 AN: 39676

South Asian (SAS) AF: 0.307 AC: 26329 AN: 85816

European-Finnish (FIN) AF: 0.224 AC: 11933 AN: 53310

Middle Eastern (MID) AF: 0.167 AC: 960 AN: 5732

European-Non Finnish (NFE) AF: 0.110 AC: 121955 AN: 1110346

Other (OTH) AF: 0.135 AC: 8141 AN: 60186

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

African (AFR) AF: 0.0890 AC: 3697 AN: 41538

American (AMR) AF: 0.138 AC: 2114 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1442 AN: 4806

European-Finnish (FIN) AF: 0.232 AC: 2450 AN: 10564

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7769 AN: 68016

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.121 Hom.: 321

Bravo AF: 0.117

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Arrhythmogenic right ventricular dysplasia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.089
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: rs10997691; hg19: chr10-69281585; COSMIC: COSV107360434; COSMIC: COSV107360434;