rs17511

Positions:

• chr10-66319747-G-A

Variant summary

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

The NM_013266.4(CTNNA3):​c.1733-39126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,836 control chromosomes in the GnomAD database, including 25,748 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 0.57 (25748 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1733-39126C>T		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1733-39126C>T		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87183 AN: 151720 Hom.: 25733 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.575 AC: 87232 AN: 151836 Hom.: 25748 Cov.: 32 AF XY: 0.572 AC XY: 42439 AN XY: 74198

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.583

Alfa AF: 0.616 Hom.: 36356

Bravo AF: 0.577

Asia WGS AF: 0.570 AC: 1982 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.60

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: rs17511; hg19: chr10-68079505;