chr10-67504839-G-C

Variant names:

• chr10-67504839-G-C
• rs10823051
• NM_013266.4:c.579+17003C>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.579+17003C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,134 control chromosomes in the GnomAD database, including 1,622 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 0.13 (1622 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.579+17003C>G		intron_variant	Intron 5 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.579+17003C>G		intron_variant	Intron 5 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19948 AN: 152016 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.131 AC: 19953 AN: 152134 Hom.: 1622 Cov.: 32 AF XY: 0.141 AC XY: 10450 AN XY: 74358

African (AFR) AF: 0.0895 AC: 3716 AN: 41528

American (AMR) AF: 0.138 AC: 2110 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1613 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2449 AN: 10538

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7768 AN: 67998

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.131 Hom.: 176

Bravo AF: 0.117

Asia WGS AF: 0.253 AC: 880 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.49
PhyloP100		-1.2
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: rs10823051; hg19: chr10-69264597;