rs997225

Positions:

• chr10-66523212-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1375-2439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,048 control chromosomes in the GnomAD database, including 5,375 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 0.24 (5375 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1375-2439G>A		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1375-2439G>A		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36289 AN: 151930 Hom.: 5370 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.239 AC: 36329 AN: 152048 Hom.: 5375 Cov.: 32 AF XY: 0.247 AC XY: 18327 AN XY: 74318

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.242

Alfa AF: 0.231 Hom.: 9192

Bravo AF: 0.236

Asia WGS AF: 0.493 AC: 1711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs997225; hg19: chr10-68282970;