rs2126750

Positions:

• chr10-66077945-T-A

Variant summary

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

The NM_013266.4(CTNNA3):​c.1978-8456A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,562 control chromosomes in the GnomAD database, including 6,894 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 0.29 (6894 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1978-8456A>T		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1978-8456A>T		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43219 AN: 151446 Hom.: 6893 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.285 AC: 43235 AN: 151562 Hom.: 6894 Cov.: 31 AF XY: 0.287 AC XY: 21270 AN XY: 74064

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.301

Alfa AF: 0.295 Hom.: 917

Bravo AF: 0.272

Asia WGS AF: 0.437 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.56

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: rs2126750; hg19: chr10-67837703;