rs10997482

Variant names:

• chr10-67011845-G-A
• rs10997482
• NM_013266.4:c.1047+168472C>T

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+168472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,892 control chromosomes in the GnomAD database, including 11,493 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 0.38 (11493 hom., cov: 30)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 5 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]

ENSG00000302985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 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+168472C>T		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1536+83393G>A		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+168472C>T		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+168472C>T		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+83393G>A		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1047+168472C>T		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57890 AN: 151776 Hom.: 11494 Cov.: 30

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.381 AC: 57907 AN: 151892 Hom.: 11493 Cov.: 30 AF XY: 0.381 AC XY: 28282 AN XY: 74218

African (AFR) AF: 0.293 AC: 12132 AN: 41416

American (AMR) AF: 0.363 AC: 5540 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1907 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1135 AN: 5144

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4822

European-Finnish (FIN) AF: 0.478 AC: 5042 AN: 10538

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29197 AN: 67932

Other (OTH) AF: 0.416 AC: 879 AN: 2114

Alfa AF: 0.423 Hom.: 23543

Bravo AF: 0.372

Asia WGS AF: 0.292 AC: 1016 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.24
PhyloP100		0.41
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: rs10997482; hg19: chr10-68771603; COSMIC: COSV63669584; COSMIC: COSV63669584;