10-66476943-G-T

Position:

• chr10-66476943-G-T

Variant summary

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

The NM_013266.4(CTNNA3):​c.1531+43674C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,018 control chromosomes in the GnomAD database, including 607 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 0.062 (607 hom., cov: 33)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

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 (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1531+43674C>A		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+43674C>A		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9386 AN: 151902 Hom.: 606 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0393

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

GnomAD4 genome AF: 0.0619 AC: 9414 AN: 152018 Hom.: 607 Cov.: 33 AF XY: 0.0602 AC XY: 4479 AN XY: 74348

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.0555

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0218 Hom.: 44

Bravo AF: 0.0657

Asia WGS AF: 0.0720 AC: 248 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	6.0
DANN	Benign	0.45

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: rs10997162; hg19: chr10-68236701;