chr10-66465128-A-G

Position:

• chr10-66465128-A-G

Variant summary

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

The NM_013266.4(CTNNA3):​c.1531+55489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,024 control chromosomes in the GnomAD database, including 6,533 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 0.21 (6533 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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 (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1531+55489T>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+55489T>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32171 AN: 151904 Hom.: 6510 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.212 AC: 32256 AN: 152024 Hom.: 6533 Cov.: 32 AF XY: 0.219 AC XY: 16250 AN XY: 74320

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.186

Alfa AF: 0.0895 Hom.: 3147

Bravo AF: 0.231

Asia WGS AF: 0.596 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.82

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: rs2441727; hg19: chr10-68224886;