rs10997034

Variant names:

• chr10-66280482-G-T
• rs10997034
• NM_013266.4:c.1872C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013266.4(CTNNA3):​c.1872C>A​(p.Val624Val) 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:6
• Conservation: PhyloP100: 1.29
• Publications: 6 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 -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 VariationId is 415368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1872C>A	p.Val624Val	synonymous	Exon 13 of 18	NP_037398.2
	CTNNA3	NM_001127384.3		c.1872C>A	p.Val624Val	synonymous	Exon 13 of 18	NP_001120856.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1872C>A	p.Val624Val	synonymous	Exon 13 of 18	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1872C>A	p.Val624Val	synonymous	Exon 14 of 19	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1872C>A	p.Val624Val	synonymous	Exon 13 of 18	ENSP00000508371.1

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

GnomAD2 exomes AF: 0.0342 AC: 8270 AN: 241960 AF XY: 0.0355

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 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

African (AFR) AF: 0.110 AC: 3569 AN: 32492

American (AMR) AF: 0.0125 AC: 540 AN: 43256

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 1657 AN: 25918

East Asian (EAS) AF: 0.0553 AC: 2159 AN: 39022

South Asian (SAS) AF: 0.0814 AC: 6893 AN: 84704

European-Finnish (FIN) AF: 0.00700 AC: 368 AN: 52590

Middle Eastern (MID) AF: 0.0644 AC: 369 AN: 5726

European-Non Finnish (NFE) AF: 0.0154 AC: 17109 AN: 1108132

Other (OTH) AF: 0.0356 AC: 2134 AN: 59940

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

African (AFR) AF: 0.109 AC: 4525 AN: 41504

American (AMR) AF: 0.0204 AC: 310 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3466

East Asian (EAS) AF: 0.0577 AC: 298 AN: 5164

South Asian (SAS) AF: 0.0892 AC: 430 AN: 4820

European-Finnish (FIN) AF: 0.00538 AC: 57 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0176 AC: 1194 AN: 67962

Other (OTH) AF: 0.0404 AC: 85 AN: 2106

Alfa AF: 0.0289 Hom.: 178

Bravo AF: 0.0488

Asia WGS AF: 0.0960 AC: 333 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Arrhythmogenic right ventricular dysplasia 13 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		1.3
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: rs10997034; hg19: chr10-68040240;