NM_013266.4:c.1047+179356G>A

Variant names:

• chr10-67000961-C-T
• rs10997477
• NM_013266.4:c.1047+179356G>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.1047+179356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,624 control chromosomes in the GnomAD database, including 7,732 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 0.31 (7732 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• 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]

ENSG00000302985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+179356G>A		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1536+72509C>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.1047+179356G>A		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1536+72509C>T		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47427 AN: 151506 Hom.: 7732 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.313 AC: 47440 AN: 151624 Hom.: 7732 Cov.: 31 AF XY: 0.314 AC XY: 23266 AN XY: 74084

African (AFR) AF: 0.238 AC: 9844 AN: 41336

American (AMR) AF: 0.315 AC: 4795 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1129 AN: 5122

South Asian (SAS) AF: 0.266 AC: 1278 AN: 4810

European-Finnish (FIN) AF: 0.391 AC: 4102 AN: 10502

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23496 AN: 67874

Other (OTH) AF: 0.343 AC: 720 AN: 2100

Alfa AF: 0.334 Hom.: 5291

Bravo AF: 0.308

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.45
DANN	Benign	0.72
PhyloP100		-0.57
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: rs10997477; hg19: chr10-68760719;