10-67539960-A-G

Position:

• chr10-67539960-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000433211.7(CTNNA3):​c.293-291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,098 control chromosomes in the GnomAD database, including 4,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (4961 hom., cov: 32)
• Consequence: CTNNA3 ENST00000433211.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-67539960-A-G is Benign according to our data. Variant chr10-67539960-A-G is described in ClinVar as [Benign]. Clinvar id is 1221723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.293-291T>C		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.293-291T>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30030 AN: 151980 Hom.: 4926 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.198 AC: 30118 AN: 152098 Hom.: 4961 Cov.: 32 AF XY: 0.194 AC XY: 14398 AN XY: 74352

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.164

Alfa AF: 0.132 Hom.: 1023

Bravo AF: 0.208

Asia WGS AF: 0.121 AC: 422 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.71

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: rs2133696; hg19: chr10-69299718;