rs1925574

Variant names:

• chr10-66931441-C-T
• rs1925574
• NM_013266.4:c.1048-155917G>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.1048-155917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,176 control chromosomes in the GnomAD database, including 54,010 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 0.84 (54010 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 7 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]

LOC101928961 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1048-155917G>A		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1536+2989C>T		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1048-155917G>A		intron	N/A	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1048-155917G>A		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+2989C>T		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1048-155917G>A		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127811 AN: 152058 Hom.: 53947 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.841 AC: 127935 AN: 152176 Hom.: 54010 Cov.: 32 AF XY: 0.842 AC XY: 62671 AN XY: 74396

African (AFR) AF: 0.770 AC: 31937 AN: 41486

American (AMR) AF: 0.891 AC: 13631 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5155 AN: 5172

South Asian (SAS) AF: 0.927 AC: 4476 AN: 4826

European-Finnish (FIN) AF: 0.793 AC: 8391 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58511 AN: 68024

Other (OTH) AF: 0.855 AC: 1808 AN: 2114

Alfa AF: 0.860 Hom.: 67589

Bravo AF: 0.843

Asia WGS AF: 0.949 AC: 3293 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		1.2
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: rs1925574; hg19: chr10-68691199;