rs2251000

chr10-67065013-A-Gchr10-67065013-A-T

Variant summary

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

The NM_013266.4(CTNNA3):c.1047+115304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,972 control chromosomes in the GnomAD database, including 31,383 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 0.63 (31383 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1047+115304T>C		intron_variant		ENST00000433211.7
LRRTM3	NM_178011.5	c.1537-32574A>G		intron_variant		ENST00000361320.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1537-32574A>G		intron_variant		1	NM_178011.5	P1
CTNNA3	ENST00000433211.7	c.1047+115304T>C		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95689 AN: 151854 Hom.: 31339 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.630 AC: 95782 AN: 151972 Hom.: 31383 Cov.: 31 AF XY: 0.631 AC XY: 46870 AN XY: 74222

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.626

Alfa AF: 0.588 Hom.: 4231

Bravo AF: 0.635

Asia WGS AF: 0.584 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.80
Dann	Benign	0.76

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: rs2251000; hg19: chr10-68824771;