rs1925576

Variant names:

• chr10-66929325-A-G
• rs1925576
• NM_013266.4:c.1048-153801T>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.1048-153801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,038 control chromosomes in the GnomAD database, including 10,941 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 0.36 (10941 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 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.1048-153801T>C		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1536+873A>G		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1048-153801T>C		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.1048-153801T>C		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+873A>G		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1048-153801T>C		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54987 AN: 151922 Hom.: 10940 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.362 AC: 54990 AN: 152038 Hom.: 10941 Cov.: 32 AF XY: 0.362 AC XY: 26879 AN XY: 74322

African (AFR) AF: 0.204 AC: 8453 AN: 41486

American (AMR) AF: 0.362 AC: 5524 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3470

East Asian (EAS) AF: 0.154 AC: 794 AN: 5168

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4947 AN: 10570

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30898 AN: 67938

Other (OTH) AF: 0.370 AC: 779 AN: 2108

Alfa AF: 0.417 Hom.: 46071

Bravo AF: 0.342

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.43
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: rs1925576; hg19: chr10-68689083;