chr10-66223200-G-A

Position:

• chr10-66223200-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.1884+57270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,628 control chromosomes in the GnomAD database, including 22,915 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 0.54 (22915 hom., cov: 30)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1884+57270C>T		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1884+57270C>T		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81872 AN: 151508 Hom.: 22900 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.540 AC: 81910 AN: 151628 Hom.: 22915 Cov.: 30 AF XY: 0.547 AC XY: 40524 AN XY: 74050

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.552

Alfa AF: 0.573 Hom.: 5167

Bravo AF: 0.528

Asia WGS AF: 0.586 AC: 2028 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.62

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: rs922347; hg19: chr10-67982958;