rs1925574

Variant names:

• chr10-66931441-C-T
• rs1925574
• NM_013266.4:c.1048-155917G>A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1048-155917G>A		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1536+2989C>T		intron_variant	Intron 2 of 2	ENST00000361320.5	NP_821079.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1048-155917G>A		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1536+2989C>T		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

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

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.855

Alfa AF: 0.862 Hom.: 57588

Bravo AF: 0.843

Asia WGS AF: 0.949 AC: 3293 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.75

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: rs1925574; hg19: chr10-68691199;