10-67650428-T-C

Variant names:

• chr10-67650428-T-C
• rs3096244
• NM_013266.4:c.-5-2910A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.-5-2910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,974 control chromosomes in the GnomAD database, including 26,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (26236 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 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.-5-2910A>G		intron	N/A	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.-5-2910A>G		intron	N/A	NP_001120856.1	Q9UI47-1
	CTNNA3	NM_001291133.2		c.-46-1612A>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.-5-2910A>G		intron	N/A	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.-82-1612A>G		intron	N/A	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.-1-2914A>G		intron	N/A	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83396 AN: 151856 Hom.: 26171 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83520 AN: 151974 Hom.: 26236 Cov.: 31 AF XY: 0.554 AC XY: 41135 AN XY: 74262

African (AFR) AF: 0.855 AC: 35491 AN: 41490

American (AMR) AF: 0.494 AC: 7553 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3466

East Asian (EAS) AF: 0.773 AC: 3996 AN: 5172

South Asian (SAS) AF: 0.591 AC: 2845 AN: 4810

European-Finnish (FIN) AF: 0.493 AC: 5194 AN: 10528

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25634 AN: 67922

Other (OTH) AF: 0.511 AC: 1078 AN: 2110

Alfa AF: 0.466 Hom.: 27678

Bravo AF: 0.563

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		-0.40
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: rs3096244; hg19: chr10-69410186;