rs1952060

Variant names:

• chr10-67043176-T-C
• rs1952060
• NM_013266.4:c.1047+137141A>G

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+137141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 148,590 control chromosomes in the GnomAD database, including 15,714 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 0.45 (15714 hom., cov: 24)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+137141A>G		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1537-54411T>C		intron_variant	Intron 2 of 2	ENST00000361320.5	NP_821079.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1047+137141A>G		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1537-54411T>C		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67253 AN: 148512 Hom.: 15708 Cov.: 24

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.453 AC: 67278 AN: 148590 Hom.: 15714 Cov.: 24 AF XY: 0.451 AC XY: 32582 AN XY: 72260

African (AFR) AF: 0.454 AC: 18279 AN: 40292

American (AMR) AF: 0.416 AC: 6222 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2014 AN: 3446

East Asian (EAS) AF: 0.217 AC: 1103 AN: 5072

South Asian (SAS) AF: 0.469 AC: 2207 AN: 4702

European-Finnish (FIN) AF: 0.488 AC: 4682 AN: 9594

Middle Eastern (MID) AF: 0.619 AC: 177 AN: 286

European-Non Finnish (NFE) AF: 0.463 AC: 31141 AN: 67284

Other (OTH) AF: 0.483 AC: 995 AN: 2060

Alfa AF: 0.470 Hom.: 29530

Bravo AF: 0.452

Asia WGS AF: 0.374 AC: 1302 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		-0.077
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: rs1952060; hg19: chr10-68802934;