rs10491057

Variant names:

• chr10-66885462-G-A
• rs10491057
• NM_013266.4:c.1048-109938C>T

Variant summary

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

The NM_013266.4(CTNNA3):​c.1048-109938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,028 control chromosomes in the GnomAD database, including 180 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 0.025 (180 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1048-109938C>T		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.1048-109938C>T		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3823 AN: 151910 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.00549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0252 AC: 3828 AN: 152028 Hom.: 180 Cov.: 32 AF XY: 0.0282 AC XY: 2092 AN XY: 74302

Gnomad4 AFR AF: 0.00547

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0173 Hom.: 17

Bravo AF: 0.0286

Asia WGS AF: 0.159 AC: 552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.071
DANN	Benign	0.46

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: rs10491057; hg19: chr10-68645220;