NM_013266.4:c.1048-201259A>G

Variant names:

• chr10-66976783-T-C
• rs942780
• NM_013266.4:c.1048-201259A>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.1048-201259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,180 control chromosomes in the GnomAD database, including 3,183 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 0.20 (3183 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1048-201259A>G		intron	N/A	NP_037398.2	Q9UI47-1
	LRRTM3	NM_178011.5	MANE Select	c.1536+48331T>C		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1048-201259A>G		intron	N/A	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1048-201259A>G		intron	N/A	ENSP00000389714.1	Q9UI47-1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+48331T>C		intron	N/A	ENSP00000355187.3	Q86VH5-1
	CTNNA3	ENST00000682758.1		c.1048-201259A>G		intron	N/A	ENSP00000508047.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30532 AN: 152062 Hom.: 3183 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.201 AC: 30528 AN: 152180 Hom.: 3183 Cov.: 32 AF XY: 0.205 AC XY: 15234 AN XY: 74368

African (AFR) AF: 0.184 AC: 7629 AN: 41534

American (AMR) AF: 0.181 AC: 2765 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5166

South Asian (SAS) AF: 0.172 AC: 827 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3045 AN: 10570

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13165 AN: 68020

Other (OTH) AF: 0.210 AC: 443 AN: 2114

Alfa AF: 0.193 Hom.: 598

Bravo AF: 0.196

Asia WGS AF: 0.271 AC: 942 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		0.12
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: rs942780; hg19: chr10-68736541;