10-67096446-G-T

Position:

• chr10-67096446-G-T

Variant summary

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

The ENST00000433211.7(CTNNA3):​c.1047+83871C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,608 control chromosomes in the GnomAD database, including 24,730 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 0.56 (24730 hom., cov: 31)
• Consequence: CTNNA3 ENST00000433211.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+83871C>A		intron_variant		ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1537-1141G>T		intron_variant		ENST00000361320.5	NP_821079.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1537-1141G>T		intron_variant		1	NM_178011.5	ENSP00000355187	P1
CTNNA3	ENST00000433211.7	c.1047+83871C>A		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84090 AN: 151490 Hom.: 24693 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.555 AC: 84176 AN: 151608 Hom.: 24730 Cov.: 31 AF XY: 0.556 AC XY: 41187 AN XY: 74100

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.556

Alfa AF: 0.500 Hom.: 4039

Bravo AF: 0.565

Asia WGS AF: 0.490 AC: 1704 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.28

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: rs10762138; hg19: chr10-68856204;