10-66990654-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013266.4(CTNNA3):​c.1047+189663T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,866 control chromosomes in the GnomAD database, including 18,297 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 0.48 ( 18297 hom., cov: 32)

Consequence

CTNNA3
NM_013266.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTNNA3NM_013266.4 linkuse as main transcriptc.1047+189663T>G intron_variant ENST00000433211.7 NP_037398.2
LRRTM3NM_178011.5 linkuse as main transcriptc.1536+62202A>C intron_variant ENST00000361320.5 NP_821079.3
LOC101928961NR_111911.1 linkuse as main transcriptn.92-6350T>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRTM3ENST00000361320.5 linkuse as main transcriptc.1536+62202A>C intron_variant 1 NM_178011.5 ENSP00000355187 P1Q86VH5-1
CTNNA3ENST00000433211.7 linkuse as main transcriptc.1047+189663T>G intron_variant 1 NM_013266.4 ENSP00000389714 P1Q9UI47-1

Frequencies

GnomAD3 genomes
AF:
0.483
AC:
73244
AN:
151746
Hom.:
18265
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.581
Gnomad AMI
AF:
0.333
Gnomad AMR
AF:
0.554
Gnomad ASJ
AF:
0.330
Gnomad EAS
AF:
0.484
Gnomad SAS
AF:
0.363
Gnomad FIN
AF:
0.432
Gnomad MID
AF:
0.290
Gnomad NFE
AF:
0.434
Gnomad OTH
AF:
0.466
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.483
AC:
73320
AN:
151866
Hom.:
18297
Cov.:
32
AF XY:
0.479
AC XY:
35520
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.581
Gnomad4 AMR
AF:
0.555
Gnomad4 ASJ
AF:
0.330
Gnomad4 EAS
AF:
0.483
Gnomad4 SAS
AF:
0.364
Gnomad4 FIN
AF:
0.432
Gnomad4 NFE
AF:
0.434
Gnomad4 OTH
AF:
0.460
Alfa
AF:
0.428
Hom.:
28558
Bravo
AF:
0.498
Asia WGS
AF:
0.397
AC:
1383
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
5.3
DANN
Benign
0.95

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1925608; hg19: chr10-68750412; API