10-66799042-A-G

Position:

• chr10-66799042-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.1048-23518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,462 control chromosomes in the GnomAD database, including 5,309 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 0.25 (5309 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1048-23518T>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.1048-23518T>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37284 AN: 151344 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.246 AC: 37311 AN: 151462 Hom.: 5309 Cov.: 32 AF XY: 0.245 AC XY: 18118 AN XY: 74050

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.206

Alfa AF: 0.132 Hom.: 351

Bravo AF: 0.252

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.38

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: rs7089541; hg19: chr10-68558800;