10-66930145-C-T

Variant names:

• chr10-66930145-C-T
• rs1925575
• NM_013266.4:c.1048-154621G>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.1048-154621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,974 control chromosomes in the GnomAD database, including 12,456 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 0.40 (12456 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1048-154621G>A		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1536+1693C>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.1048-154621G>A		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1536+1693C>T		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60950 AN: 151856 Hom.: 12428 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.402 AC: 61027 AN: 151974 Hom.: 12456 Cov.: 32 AF XY: 0.400 AC XY: 29747 AN XY: 74288

African (AFR) AF: 0.423 AC: 17526 AN: 41436

American (AMR) AF: 0.470 AC: 7177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2410 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2212 AN: 4810

European-Finnish (FIN) AF: 0.294 AC: 3103 AN: 10550

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25511 AN: 67944

Other (OTH) AF: 0.423 AC: 895 AN: 2114

Alfa AF: 0.408 Hom.: 2257

Bravo AF: 0.418

Asia WGS AF: 0.441 AC: 1528 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.43
PhyloP100		-0.25
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: rs1925575; hg19: chr10-68689903;