rs1916389

Variant names:

• chr10-66956230-T-C
• rs1916389
• NM_013266.4:c.1048-180706A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1048-180706A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 150,816 control chromosomes in the GnomAD database, including 2,261 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 0.17 (2261 hom., cov: 30)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 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.1048-180706A>G		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1536+27778T>C		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1048-180706A>G		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.1048-180706A>G		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+27778T>C		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1048-180706A>G		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25390 AN: 150696 Hom.: 2261 Cov.: 30

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.168 AC: 25387 AN: 150816 Hom.: 2261 Cov.: 30 AF XY: 0.167 AC XY: 12289 AN XY: 73532

African (AFR) AF: 0.167 AC: 6869 AN: 41050

American (AMR) AF: 0.142 AC: 2129 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5170

South Asian (SAS) AF: 0.0732 AC: 349 AN: 4768

European-Finnish (FIN) AF: 0.236 AC: 2438 AN: 10340

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12478 AN: 67782

Other (OTH) AF: 0.184 AC: 381 AN: 2072

Alfa AF: 0.177 Hom.: 7730

Bravo AF: 0.163

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		0.15
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: rs1916389; hg19: chr10-68715988;