rs2306402

Positions:

• chr10-67175727-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.1047+4590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,992 control chromosomes in the GnomAD database, including 14,580 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 0.37 (14580 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1047+4590G>A		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1047+4590G>A		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55506 AN: 151874 Hom.: 14537 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.366 AC: 55600 AN: 151992 Hom.: 14580 Cov.: 32 AF XY: 0.366 AC XY: 27197 AN XY: 74298

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.326

Alfa AF: 0.313 Hom.: 1706

Bravo AF: 0.378

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
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: rs2306402; hg19: chr10-68935485;