rs10822988

Variant names:

• chr10-67154882-A-G
• rs10822988
• NM_013266.4:c.1047+25435T>C

Variant summary

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

The NM_013266.4(CTNNA3):​c.1047+25435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,974 control chromosomes in the GnomAD database, including 31,636 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 0.63 (31636 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+25435T>C		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1047+25435T>C		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96129 AN: 151856 Hom.: 31609 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.633 AC: 96209 AN: 151974 Hom.: 31636 Cov.: 31 AF XY: 0.637 AC XY: 47301 AN XY: 74288

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.640

Alfa AF: 0.604 Hom.: 3654

Bravo AF: 0.636

Asia WGS AF: 0.540 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.79

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: rs10822988; hg19: chr10-68914640;