NM_013266.4:c.1047+83871C>A

Variant names:

• chr10-67096446-G-T
• rs10762138
• NM_013266.4:c.1047+83871C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1047+83871C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,608 control chromosomes in the GnomAD database, including 24,730 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 0.56 (24730 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 2 publications found

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]

LRRTM3 (HGNC:19410): (leucine rich repeat transmembrane neuronal 3) Involved in presynapse assembly. Acts upstream of or within positive regulation of amyloid-beta formation. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1047+83871C>A		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1537-1141G>T		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+83871C>A		intron	N/A	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1047+83871C>A		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1537-1141G>T		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1047+83871C>A		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84090 AN: 151490 Hom.: 24693 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.555 AC: 84176 AN: 151608 Hom.: 24730 Cov.: 31 AF XY: 0.556 AC XY: 41187 AN XY: 74100

African (AFR) AF: 0.760 AC: 31482 AN: 41402

American (AMR) AF: 0.466 AC: 7074 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2213 AN: 3460

East Asian (EAS) AF: 0.510 AC: 2608 AN: 5116

South Asian (SAS) AF: 0.438 AC: 2111 AN: 4816

European-Finnish (FIN) AF: 0.540 AC: 5702 AN: 10562

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31227 AN: 67754

Other (OTH) AF: 0.556 AC: 1170 AN: 2106

Alfa AF: 0.507 Hom.: 4268

Bravo AF: 0.565

Asia WGS AF: 0.490 AC: 1704 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.28
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10762138; hg19: chr10-68856204;