rs17279006

Positions:

• chr10-66998988-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+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

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]

LOC101928961 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1047+181329T>C		intron_variant		ENST00000433211.7
LRRTM3	NM_178011.5	c.1536+70536A>G		intron_variant		ENST00000361320.5
LOC101928961	NR_111911.1	n.91+13075T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1536+70536A>G		intron_variant		1	NM_178011.5	P1
CTNNA3	ENST00000433211.7	c.1047+181329T>C		intron_variant		1	NM_013266.4	P1

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

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0366

Gnomad4 FIN AF: 0.0878

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0384 Hom.: 41

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

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: rs17279006; hg19: chr10-68758746;