8-97776094-G-C

Variant summary

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

The NM_018407.6(LAPTM4B):ā€‹c.85G>Cā€‹(p.Gly29Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,581,844 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

LAPTM4B
NM_018407.6 missense

Scores

8
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45
Variant links:
Genes affected
LAPTM4B (HGNC:13646): (lysosomal protein transmembrane 4 beta) Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including negative regulation of macromolecule metabolic process; regulation of lysosomal membrane permeability; and regulation of lysosome organization. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.875

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LAPTM4BNM_018407.6 linkc.85G>C p.Gly29Arg missense_variant 1/7 ENST00000521545.7 NP_060877.4 Q86VI4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LAPTM4BENST00000521545.7 linkc.85G>C p.Gly29Arg missense_variant 1/71 NM_018407.6 ENSP00000428409.1 Q86VI4-2
LAPTM4BENST00000445593.6 linkc.358G>C p.Gly120Arg missense_variant 1/71 ENSP00000402301.2 Q86VI4-3
LAPTM4BENST00000619747.1 linkc.358G>C p.Gly120Arg missense_variant 1/71 ENSP00000482533.1 Q86VI4-3
LAPTM4BENST00000517924.5 linkc.85G>C p.Gly29Arg missense_variant 1/55 ENSP00000429868.2 H0YBN1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152238
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:
0.0000298
AC:
6
AN:
201454
Hom.:
0
AF XY:
0.0000266
AC XY:
3
AN XY:
112994
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:
0.000210
Gnomad NFE exome
AF:
0.0000332
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000336
AC:
48
AN:
1429606
Hom.:
0
Cov.:
34
AF XY:
0.0000365
AC XY:
26
AN XY:
711522
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:
0.0000914
Gnomad4 NFE exome
AF:
0.0000390
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74380
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:
0.000211
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000418
AC:
5

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 20, 2022The c.358G>C (p.G120R) alteration is located in exon 1 (coding exon 1) of the LAPTM4B gene. This alteration results from a G to C substitution at nucleotide position 358, causing the glycine (G) at amino acid position 120 to be replaced by an arginine (R). 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
0.99
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
.;.;.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;.;D;D
M_CAP
Pathogenic
0.48
D
MetaRNN
Pathogenic
0.88
D;D;D;D
MetaSVM
Uncertain
-0.21
T
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-7.1
.;D;D;.
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0010
.;D;D;.
Sift4G
Uncertain
0.0020
D;D;D;D
Vest4
0.96
MVP
0.77
MPC
1.1
ClinPred
0.94
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.81
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs760412892; hg19: chr8-98788322; API