chr10-67060694-T-C

Variant names:

• chr10-67060694-T-C
• rs1925594
• NM_013266.4:c.1047+119623A>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.1047+119623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,082 control chromosomes in the GnomAD database, including 1,822 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 0.13 (1822 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+119623A>G		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1537-36893T>C		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+119623A>G		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1537-36893T>C		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20393 AN: 151962 Hom.: 1815 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.134 AC: 20418 AN: 152082 Hom.: 1822 Cov.: 32 AF XY: 0.136 AC XY: 10096 AN XY: 74348

African (AFR) AF: 0.254 AC: 10545 AN: 41480

American (AMR) AF: 0.0686 AC: 1047 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5158

South Asian (SAS) AF: 0.136 AC: 654 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1070 AN: 10604

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5863 AN: 67968

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.132 Hom.: 214

Bravo AF: 0.134

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.40
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: rs1925594; hg19: chr10-68820452;