10-67009880-G-A

Variant names:

• chr10-67009880-G-A
• rs1925622
• NM_013266.4:c.1047+170437C>T

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+170437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,908 control chromosomes in the GnomAD database, including 19,799 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 0.49 (19799 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• 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]

ENSG00000302985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 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.1047+170437C>T		intron	N/A	NP_037398.2
	LRRTM3	NM_178011.5	MANE Select	c.1536+81428G>A		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+170437C>T		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.1047+170437C>T		intron	N/A	ENSP00000389714.1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+81428G>A		intron	N/A	ENSP00000355187.3
	CTNNA3	ENST00000682758.1		c.1047+170437C>T		intron	N/A	ENSP00000508047.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75174 AN: 151788 Hom.: 19804 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.495 AC: 75188 AN: 151908 Hom.: 19799 Cov.: 32 AF XY: 0.498 AC XY: 36939 AN XY: 74236

African (AFR) AF: 0.340 AC: 14094 AN: 41428

American (AMR) AF: 0.467 AC: 7120 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2357 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1179 AN: 5154

South Asian (SAS) AF: 0.596 AC: 2872 AN: 4818

European-Finnish (FIN) AF: 0.622 AC: 6554 AN: 10542

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39138 AN: 67932

Other (OTH) AF: 0.541 AC: 1139 AN: 2106

Alfa AF: 0.501 Hom.: 3613

Bravo AF: 0.475

Asia WGS AF: 0.428 AC: 1489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.45
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1925622; hg19: chr10-68769638;