10-66624215-T-C

Variant names:

• chr10-66624215-T-C
• rs10822856
• NM_013266.4:c.1282-2431A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1282-2431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,888 control chromosomes in the GnomAD database, including 8,825 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 0.33 (8825 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1282-2431A>G		intron_variant	Intron 9 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1282-2431A>G		intron_variant	Intron 9 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50518 AN: 151766 Hom.: 8822 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.333 AC: 50542 AN: 151888 Hom.: 8825 Cov.: 31 AF XY: 0.333 AC XY: 24735 AN XY: 74202

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.345

Alfa AF: 0.330 Hom.: 3448

Bravo AF: 0.341

Asia WGS AF: 0.343 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.062
DANN	Benign	0.39

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: rs10822856; hg19: chr10-68383973;