rs1925608

Variant names:

• chr10-66990654-A-C
• rs1925608
• NM_013266.4:c.1047+189663T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-66990654-A-C
• chr10-66990654-A-G
• chr10-66990654-A-T

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+189663T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,866 control chromosomes in the GnomAD database, including 18,297 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 0.48 (18297 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 6 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 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+189663T>G		intron	N/A	NP_037398.2	Q9UI47-1
	LRRTM3	NM_178011.5	MANE Select	c.1536+62202A>C		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+189663T>G		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+189663T>G		intron	N/A	ENSP00000389714.1	Q9UI47-1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+62202A>C		intron	N/A	ENSP00000355187.3	Q86VH5-1
	CTNNA3	ENST00000682758.1		c.1047+189663T>G		intron	N/A	ENSP00000508047.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73244 AN: 151746 Hom.: 18265 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.483 AC: 73320 AN: 151866 Hom.: 18297 Cov.: 32 AF XY: 0.479 AC XY: 35520 AN XY: 74208

African (AFR) AF: 0.581 AC: 24043 AN: 41368

American (AMR) AF: 0.555 AC: 8469 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2496 AN: 5168

South Asian (SAS) AF: 0.364 AC: 1753 AN: 4820

European-Finnish (FIN) AF: 0.432 AC: 4546 AN: 10528

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29509 AN: 67944

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.443 Hom.: 63728

Bravo AF: 0.498

Asia WGS AF: 0.397 AC: 1383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.3
DANN	Benign	0.95
PhyloP100		0.30
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: rs1925608; hg19: chr10-68750412;