1-110401551-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001382293.1(LAMTOR5):​c.248C>T​(p.Thr83Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000578 in 1,607,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LAMTOR5
NM_001382293.1 missense

Scores

10
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.51
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMTOR5NM_001382293.1 linkc.248C>T p.Thr83Met missense_variant Exon 4 of 4 ENST00000602318.6 NP_001369222.1
LAMTOR5NM_006402.3 linkc.494C>T p.Thr165Met missense_variant Exon 4 of 4 NP_006393.2 O43504A0A8Z5A536

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMTOR5ENST00000602318.6 linkc.248C>T p.Thr83Met missense_variant Exon 4 of 4 1 NM_001382293.1 ENSP00000473439.1 O43504

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251234
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
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:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000618
AC:
90
AN:
1455552
Hom.:
0
Cov.:
30
AF XY:
0.0000567
AC XY:
41
AN XY:
722684
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000741
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 GeneticsSep 27, 2024The c.494C>T (p.T165M) alteration is located in exon 4 (coding exon 4) of the LAMTOR5 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the threonine (T) at amino acid position 165 to be replaced by a methionine (M). 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
0.70
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.34
T;T;T;.;T;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
.;D;D;.;D;D
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.85
D;D;D;D;D;D
MetaSVM
Uncertain
-0.065
T
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-4.3
D;D;.;D;.;.
REVEL
Pathogenic
0.81
Sift
Uncertain
0.0020
D;D;.;D;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
0.88
MVP
0.71
MPC
0.88
ClinPred
0.83
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.80

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: rs200317420; hg19: chr1-110944173; COSMIC: COSV56678791; COSMIC: COSV56678791; API