chr10-67492583-A-G

Variant names:

• chr10-67492583-A-G
• rs12253240
• NM_013266.4:c.579+29259T>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.579+29259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 152,250 control chromosomes in the GnomAD database, including 479 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 0.072 (479 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 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.579+29259T>C		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.579+29259T>C		intron	N/A	NP_001120856.1
	CTNNA3	NM_001291133.2		c.615+29259T>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.579+29259T>C		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.579+29259T>C		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.579+29259T>C		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10943 AN: 152132 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0720 AC: 10966 AN: 152250 Hom.: 479 Cov.: 32 AF XY: 0.0719 AC XY: 5354 AN XY: 74458

African (AFR) AF: 0.113 AC: 4696 AN: 41522

American (AMR) AF: 0.0609 AC: 931 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5190

South Asian (SAS) AF: 0.140 AC: 676 AN: 4828

European-Finnish (FIN) AF: 0.0371 AC: 394 AN: 10616

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0575 AC: 3913 AN: 68008

Other (OTH) AF: 0.0633 AC: 134 AN: 2116

Alfa AF: 0.0664 Hom.: 65

Bravo AF: 0.0720

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.69
PhyloP100		0.21
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: rs12253240; hg19: chr10-69252341;