10-65920087-C-T

Variant names:

• chr10-65920087-C-T
• rs77424782
• NM_013266.4:c.*243G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013266.4(CTNNA3):​c.*243G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 519,236 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (92 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (24 hom.)
• Consequence: CTNNA3 NM_013266.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.330
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-65920087-C-T is Benign according to our data. Variant chr10-65920087-C-T is described in ClinVar as Benign. ClinVar VariationId is 1257910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 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.*243G>A		3_prime_UTR	Exon 18 of 18	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.*243G>A		3_prime_UTR	Exon 18 of 18	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.*243G>A		3_prime_UTR	Exon 18 of 18	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.*243G>A		3_prime_UTR	Exon 19 of 19	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.*243G>A		3_prime_UTR	Exon 18 of 18	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2883 AN: 152114 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00247 AC: 908 AN: 367004 Hom.: 24 Cov.: 2 AF XY: 0.00213 AC XY: 412 AN XY: 193048

African (AFR) AF: 0.0619 AC: 669 AN: 10804

American (AMR) AF: 0.00485 AC: 63 AN: 12982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11712

East Asian (EAS) AF: 0.00 AC: 0 AN: 25142

South Asian (SAS) AF: 0.000109 AC: 4 AN: 36574

European-Finnish (FIN) AF: 0.0000432 AC: 1 AN: 23132

Middle Eastern (MID) AF: 0.00306 AC: 5 AN: 1632

European-Non Finnish (NFE) AF: 0.000215 AC: 48 AN: 223466

Other (OTH) AF: 0.00547 AC: 118 AN: 21560

GnomAD4 genome AF: 0.0189 AC: 2884 AN: 152232 Hom.: 92 Cov.: 32 AF XY: 0.0176 AC XY: 1310 AN XY: 74424

African (AFR) AF: 0.0659 AC: 2736 AN: 41530

American (AMR) AF: 0.00634 AC: 97 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68014

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0124 Hom.: 11

Bravo AF: 0.0215

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

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: rs77424782; hg19: chr10-67679845;