rs10997145

Positions:

• chr10-66461549-C-G
• chr10-66461549-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.1531+59068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,518 control chromosomes in the GnomAD database, including 1,390 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 0.11 (1390 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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 = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1531+59068G>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.1531+59068G>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17220 AN: 151404 Hom.: 1384 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.114 AC: 17248 AN: 151518 Hom.: 1390 Cov.: 31 AF XY: 0.112 AC XY: 8280 AN XY: 74004

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0820

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0212 Hom.: 10

Bravo AF: 0.118

Asia WGS AF: 0.122 AC: 423 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	0.10
DANN	Benign	0.43

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: rs10997145; hg19: chr10-68221307;