NM_013266.4:c.1047+82960T>C

Variant names:

• chr10-67097357-A-G
• rs2394341
• NM_013266.4:c.1047+82960T>C

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+82960T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,650 control chromosomes in the GnomAD database, including 26,184 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 0.57 (26184 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 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+82960T>C		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1537-230A>G		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+82960T>C		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+82960T>C		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1537-230A>G		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1047+82960T>C		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85967 AN: 151534 Hom.: 26138 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.568 AC: 86064 AN: 151650 Hom.: 26184 Cov.: 32 AF XY: 0.567 AC XY: 42010 AN XY: 74076

African (AFR) AF: 0.803 AC: 33245 AN: 41410

American (AMR) AF: 0.472 AC: 7171 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2605 AN: 5122

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4814

European-Finnish (FIN) AF: 0.538 AC: 5677 AN: 10546

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

European-Non Finnish (NFE) AF: 0.461 AC: 31249 AN: 67778

Other (OTH) AF: 0.565 AC: 1193 AN: 2110

Alfa AF: 0.513 Hom.: 7722

Bravo AF: 0.580

Asia WGS AF: 0.493 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2394341; hg19: chr10-68857115;