rs2394341

Positions:

• chr10-67097357-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+82960T>C		intron_variant		ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1537-230A>G		intron_variant		ENST00000361320.5	NP_821079.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1537-230A>G		intron_variant		1	NM_178011.5	ENSP00000355187	P1
CTNNA3	ENST00000433211.7	c.1047+82960T>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

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

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.565

Alfa AF: 0.506 Hom.: 4067

Bravo AF: 0.580

Asia WGS AF: 0.493 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs2394341; hg19: chr10-68857115;