rs6480140

Positions:

• chr10-66109123-A-C
• chr10-66109123-A-G

Variant summary

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

The NM_013266.4(CTNNA3):​c.1885-5874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,030 control chromosomes in the GnomAD database, including 17,704 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 0.46 (17704 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1885-5874T>G		intron_variant		ENST00000433211.7
LOC105378340	XR_007062172.1	n.227-9130A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1885-5874T>G		intron_variant		1	NM_013266.4	P1
	ENST00000608793.1	n.486-9130A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69583 AN: 151912 Hom.: 17675 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.458 AC: 69660 AN: 152030 Hom.: 17704 Cov.: 32 AF XY: 0.456 AC XY: 33882 AN XY: 74324

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.433

Alfa AF: 0.406 Hom.: 1783

Bravo AF: 0.479

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.69

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: rs6480140; hg19: chr10-67868881;