rs17279006

Variant names:

• chr10-66998988-A-G
• rs17279006
• NM_013266.4:c.1047+181329T>C

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+181329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,258 control chromosomes in the GnomAD database, including 269 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 0.050 (269 hom., cov: 33)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 2 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]

ENSG00000302985 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+181329T>C		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1536+70536A>G		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+181329T>C		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1536+70536A>G		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7551 AN: 152140 Hom.: 269 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0496 AC: 7551 AN: 152258 Hom.: 269 Cov.: 33 AF XY: 0.0497 AC XY: 3699 AN XY: 74446

African (AFR) AF: 0.0112 AC: 464 AN: 41576

American (AMR) AF: 0.0357 AC: 546 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0366 AC: 177 AN: 4834

European-Finnish (FIN) AF: 0.0878 AC: 932 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4977 AN: 67968

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0425 Hom.: 118

Bravo AF: 0.0429

Asia WGS AF: 0.0180 AC: 62 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17279006; hg19: chr10-68758746;