1-110404034-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382293.1(LAMTOR5):​c.100C>T​(p.Arg34Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000973 in 1,613,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

LAMTOR5
NM_001382293.1 missense, splice_region

Scores

11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
Variant links:
Genes affected
LAMTOR5 (HGNC:17955): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 5) This gene encodes a protein that specifically complexes with the C-terminus of hepatitis B virus X protein (HBx). The function of this protein is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus. [provided by RefSeq, Jul 2008]
LAMTOR5-AS1 (HGNC:40823): (LAMTOR5 and SLC16A4 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMTOR5NM_001382293.1 linkc.100C>T p.Arg34Cys missense_variant, splice_region_variant Exon 3 of 4 ENST00000602318.6 NP_001369222.1
LAMTOR5NM_006402.3 linkc.346C>T p.Arg116Cys missense_variant, splice_region_variant Exon 3 of 4 NP_006393.2 O43504A0A8Z5A536

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMTOR5ENST00000602318.6 linkc.100C>T p.Arg34Cys missense_variant, splice_region_variant Exon 3 of 4 1 NM_001382293.1 ENSP00000473439.1 O43504

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000399
AC:
10
AN:
250492
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000794
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000992
AC:
145
AN:
1461376
Hom.:
0
Cov.:
30
AF XY:
0.000106
AC XY:
77
AN XY:
726986
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000123
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152086
Hom.:
0
Cov.:
32
AF XY:
0.0000808
AC XY:
6
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000992
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 05, 2023The c.346C>T (p.R116C) alteration is located in exon 3 (coding exon 3) of the LAMTOR5 gene. This alteration results from a C to T substitution at nucleotide position 346, causing the arginine (R) at amino acid position 116 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T;T;.;T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
.;T;T;.;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Uncertain
0.53
D;D;D;D;D;D
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.9
D;D;.;D;.;.
REVEL
Uncertain
0.30
Sift
Benign
0.14
T;T;.;T;.;.
Sift4G
Benign
0.15
T;T;T;T;T;T
Polyphen
0.0020
.;.;B;.;.;.
Vest4
0.60
MutPred
0.31
.;.;Gain of catalytic residue at S38 (P = 0.1038);.;.;.;
MVP
0.83
MPC
0.35
ClinPred
0.39
T
GERP RS
5.9
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
3.9
Varity_R
0.38
gMVP
0.66

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: rs753545435; hg19: chr1-110946656; COSMIC: COSV99862236; COSMIC: COSV99862236; API