rs1998753

Variant names:

• chr10-66978159-T-C
• rs1998753
• NM_013266.4:c.1047+202158A>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+202158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 151,744 control chromosomes in the GnomAD database, including 66,882 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 0.94 (66882 hom., cov: 28)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1047+202158A>G		intron_variant	Intron 7 of 17	ENST00000433211.7	NP_037398.2
LRRTM3	NM_178011.5	c.1536+49707T>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+202158A>G		intron_variant	Intron 7 of 17	1	NM_013266.4	ENSP00000389714.1
LRRTM3	ENST00000361320.5	c.1536+49707T>C		intron_variant	Intron 2 of 2	1	NM_178011.5	ENSP00000355187.3

Frequencies

GnomAD3 genomes AF: 0.935 AC: 141830 AN: 151626 Hom.: 66836 Cov.: 28

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.971

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.935 AC: 141933 AN: 151744 Hom.: 66882 Cov.: 28 AF XY: 0.938 AC XY: 69560 AN XY: 74130

African (AFR) AF: 0.808 AC: 33324 AN: 41246

American (AMR) AF: 0.977 AC: 14867 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3455 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5137 AN: 5138

South Asian (SAS) AF: 0.990 AC: 4757 AN: 4806

European-Finnish (FIN) AF: 0.988 AC: 10414 AN: 10538

Middle Eastern (MID) AF: 0.966 AC: 282 AN: 292

European-Non Finnish (NFE) AF: 0.982 AC: 66777 AN: 68008

Other (OTH) AF: 0.954 AC: 2013 AN: 2110

Alfa AF: 0.954 Hom.: 8623

Bravo AF: 0.928

Asia WGS AF: 0.986 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.61
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: rs1998753; hg19: chr10-68737917;