1-110403930-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001382293.1(LAMTOR5):​c.204A>T​(p.Glu68Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

LAMTOR5
NM_001382293.1 missense

Scores

3
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.319
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34153947).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMTOR5NM_001382293.1 linkc.204A>T p.Glu68Asp missense_variant Exon 3 of 4 ENST00000602318.6 NP_001369222.1
LAMTOR5NM_006402.3 linkc.450A>T p.Glu150Asp missense_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.204A>T p.Glu68Asp missense_variant Exon 3 of 4 1 NM_001382293.1 ENSP00000473439.1 O43504

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251288
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135828
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461766
Hom.:
0
Cov.:
30
AF XY:
0.0000358
AC XY:
26
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152224
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000453
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsDec 01, 2022The c.450A>T (p.E150D) alteration is located in exon 3 (coding exon 3) of the LAMTOR5 gene. This alteration results from a A to T substitution at nucleotide position 450, causing the glutamic acid (E) at amino acid position 150 to be replaced by an aspartic acid (D). 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
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.23
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;T;T;.;T;.
Eigen
Benign
-0.0069
Eigen_PC
Benign
-0.094
FATHMM_MKL
Benign
0.50
D
LIST_S2
Uncertain
0.86
.;D;D;.;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.34
T;T;T;T;T;T
MetaSVM
Benign
-0.72
T
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.9
D;D;.;D;.;.
REVEL
Benign
0.28
Sift
Uncertain
0.0090
D;D;.;D;.;.
Sift4G
Uncertain
0.018
D;D;D;D;D;D
Polyphen
0.98
.;.;D;.;.;.
Vest4
0.55
MutPred
0.45
.;.;Gain of catalytic residue at N73 (P = 0.2564);.;.;.;
MVP
0.81
MPC
0.74
ClinPred
0.92
D
GERP RS
-0.69
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.69
gMVP
0.69

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: rs200442714; hg19: chr1-110946552; API