rs1904648

Variant names:

• chr10-67197197-A-G
• rs1904648
• NM_013266.4:c.844-16677T>C

Variant summary

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

The NM_013266.4(CTNNA3):​c.844-16677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,976 control chromosomes in the GnomAD database, including 15,996 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 0.39 (15996 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.92
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.844-16677T>C		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.844-16677T>C		intron	N/A	NP_001120856.1
	CTNNA3	NM_001291133.2		c.880-16677T>C		intron	N/A	NP_001278062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.844-16677T>C		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.844-16677T>C		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.844-16677T>C		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58538 AN: 151858 Hom.: 15950 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.386 AC: 58638 AN: 151976 Hom.: 15996 Cov.: 32 AF XY: 0.387 AC XY: 28753 AN XY: 74294

African (AFR) AF: 0.780 AC: 32345 AN: 41468

American (AMR) AF: 0.289 AC: 4406 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1500 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2700 AN: 10582

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14082 AN: 67904

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.301 Hom.: 3353

Bravo AF: 0.405

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0020
DANN	Benign	0.41
PhyloP100		-4.9
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: rs1904648; hg19: chr10-68956955;