rs16923760

Positions:

• chr10-66920370-T-C

Variant summary

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

The NM_013266.4(CTNNA3):​c.1048-144846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,198 control chromosomes in the GnomAD database, including 1,731 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 0.12 (1731 hom., cov: 33)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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]

LOC101928961 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1048-144846A>G		intron_variant		ENST00000433211.7
LOC101928961	NR_111911.1	n.2718-9877A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1048-144846A>G		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18716 AN: 152080 Hom.: 1725 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.123 AC: 18730 AN: 152198 Hom.: 1731 Cov.: 33 AF XY: 0.127 AC XY: 9445 AN XY: 74394

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.129

Alfa AF: 0.134 Hom.: 2113

Bravo AF: 0.126

Asia WGS AF: 0.248 AC: 862 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.44

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: rs16923760; hg19: chr10-68680128;