1-110401579-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001382293.1(LAMTOR5):ā€‹c.220A>Gā€‹(p.Ile74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000028 ( 0 hom. )

Consequence

LAMTOR5
NM_001382293.1 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.112348765).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMTOR5NM_001382293.1 linkc.220A>G p.Ile74Val missense_variant Exon 4 of 4 ENST00000602318.6 NP_001369222.1
LAMTOR5NM_006402.3 linkc.466A>G p.Ile156Val 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.220A>G p.Ile74Val missense_variant Exon 4 of 4 1 NM_001382293.1 ENSP00000473439.1 O43504

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250884
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135708
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1451428
Hom.:
0
Cov.:
30
AF XY:
0.00000278
AC XY:
2
AN XY:
719592
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:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsAug 04, 2024The c.466A>G (p.I156V) alteration is located in exon 4 (coding exon 4) of the LAMTOR5 gene. This alteration results from a A to G substitution at nucleotide position 466, causing the isoleucine (I) at amino acid position 156 to be replaced by a valine (V). 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
Benign
0.083
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.011
T;T;T;.;T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.66
.;T;T;.;T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.11
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.17
N;N;.;N;.;.
REVEL
Benign
0.039
Sift
Benign
0.42
T;T;.;T;.;.
Sift4G
Benign
0.41
T;T;T;T;T;T
Polyphen
0.0060
.;.;B;.;.;.
Vest4
0.13
MutPred
0.38
.;.;Loss of ubiquitination at K78 (P = 0.1306);.;.;.;
MVP
0.70
MPC
0.22
ClinPred
0.91
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.28
gMVP
0.51

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: rs1187012460; hg19: chr1-110944201; API