rs74142830

Variant names:

• chr10-67521938-G-A
• rs74142830
• NM_013266.4:c.483C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-67521938-G-A
• chr10-67521938-G-C
• chr10-67521938-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_013266.4(CTNNA3):​c.483C>T​(p.Leu161Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 1,613,020 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: CTNNA3 NM_013266.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.118
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-67521938-G-A is Benign according to our data. Variant chr10-67521938-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 415377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.118 with no splicing effect.
• BS2: High AC in GnomAd4 at 358 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.483C>T	p.Leu161Leu	synonymous	Exon 5 of 18	NP_037398.2
	CTNNA3	NM_001127384.3		c.483C>T	p.Leu161Leu	synonymous	Exon 5 of 18	NP_001120856.1
	CTNNA3	NM_001291133.2		c.519C>T	p.Leu173Leu	synonymous	Exon 6 of 9	NP_001278062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.483C>T	p.Leu161Leu	synonymous	Exon 5 of 18	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.483C>T	p.Leu161Leu	synonymous	Exon 6 of 19	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.483C>T	p.Leu161Leu	synonymous	Exon 5 of 18	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 357 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000557 AC: 140 AN: 251154 AF XY: 0.000346

Gnomad AFR exome AF: 0.00769

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000257 AC: 376 AN: 1460730 Hom.: 1 Cov.: 31 AF XY: 0.000209 AC XY: 152 AN XY: 726690

African (AFR) AF: 0.00941 AC: 315 AN: 33460

American (AMR) AF: 0.000313 AC: 14 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111200

Other (OTH) AF: 0.000497 AC: 30 AN: 60344

GnomAD4 genome AF: 0.00235 AC: 358 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.00218 AC XY: 162 AN XY: 74456

African (AFR) AF: 0.00820 AC: 341 AN: 41570

American (AMR) AF: 0.000523 AC: 8 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00113 Hom.: 1

Bravo AF: 0.00243

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Arrhythmogenic right ventricular dysplasia 13 (1)
-	-	1	CTNNA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Benign	0.70
PhyloP100		-0.12

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: rs74142830; hg19: chr10-69281696;