10-67005059-G-T

Variant names:

• chr10-67005059-G-T
• rs1925617
• NM_013266.4:c.1047+175258C>A

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+175258C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,036 control chromosomes in the GnomAD database, including 21,588 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 0.52 (21588 hom., cov: 33)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1047+175258C>A		intron	N/A	NP_037398.2	Q9UI47-1
	LRRTM3	NM_178011.5	MANE Select	c.1536+76607G>T		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+175258C>A		intron	N/A	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1047+175258C>A		intron	N/A	ENSP00000389714.1	Q9UI47-1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+76607G>T		intron	N/A	ENSP00000355187.3	Q86VH5-1
	CTNNA3	ENST00000682758.1		c.1047+175258C>A		intron	N/A	ENSP00000508047.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79643 AN: 151918 Hom.: 21586 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.524 AC: 79672 AN: 152036 Hom.: 21588 Cov.: 33 AF XY: 0.527 AC XY: 39134 AN XY: 74304

African (AFR) AF: 0.450 AC: 18688 AN: 41492

American (AMR) AF: 0.480 AC: 7328 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2357 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5172

South Asian (SAS) AF: 0.597 AC: 2877 AN: 4816

European-Finnish (FIN) AF: 0.623 AC: 6575 AN: 10562

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38727 AN: 67942

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.539 Hom.: 3834

Bravo AF: 0.509

Asia WGS AF: 0.429 AC: 1494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.053
DANN	Benign	0.24
PhyloP100		-2.3
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: rs1925617; hg19: chr10-68764817;