rs2764807

Positions:

• chr10-67069174-T-C

Variant summary

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

The NM_013266.4(CTNNA3):​c.1047+111143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,904 control chromosomes in the GnomAD database, including 20,149 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 0.51 (20149 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+111143A>G		intron_variant		ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1537-28413T>C		intron_variant		ENST00000361320.5	NP_821079.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1537-28413T>C		intron_variant		1	NM_178011.5	ENSP00000355187	P1
CTNNA3	ENST00000433211.7	c.1047+111143A>G		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77453 AN: 151788 Hom.: 20118 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.510 AC: 77526 AN: 151904 Hom.: 20149 Cov.: 32 AF XY: 0.512 AC XY: 38055 AN XY: 74266

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.527

Alfa AF: 0.490 Hom.: 4557

Bravo AF: 0.515

Asia WGS AF: 0.477 AC: 1656 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.75

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: rs2764807; hg19: chr10-68828932;