8-97776103-T-C

Variant summary

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

The NM_018407.6(LAPTM4B):​c.94T>C​(p.Tyr32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,858 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: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LAPTM4B
NM_018407.6 missense

Scores

2
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2329551).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAPTM4BNM_018407.6 linkc.94T>C p.Tyr32His missense_variant Exon 1 of 7 ENST00000521545.7 NP_060877.4 Q86VI4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAPTM4BENST00000521545.7 linkc.94T>C p.Tyr32His missense_variant Exon 1 of 7 1 NM_018407.6 ENSP00000428409.1 Q86VI4-2
LAPTM4BENST00000445593.6 linkc.367T>C p.Tyr123His missense_variant Exon 1 of 7 1 ENSP00000402301.2 Q86VI4-3
LAPTM4BENST00000619747.1 linkc.367T>C p.Tyr123His missense_variant Exon 1 of 7 1 ENSP00000482533.1 Q86VI4-3
LAPTM4BENST00000517924.5 linkc.94T>C p.Tyr32His missense_variant Exon 1 of 5 5 ENSP00000429868.2 H0YBN1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000101
AC:
2
AN:
197960
Hom.:
0
AF XY:
0.00000898
AC XY:
1
AN XY:
111378
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000634
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000211
AC:
3
AN:
1424858
Hom.:
0
Cov.:
34
AF XY:
0.00000141
AC XY:
1
AN XY:
709106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000704
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000839
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.367T>C (p.Y123H) alteration is located in exon 1 (coding exon 1) of the LAPTM4B gene. This alteration results from a T to C substitution at nucleotide position 367, causing the tyrosine (Y) at amino acid position 123 to be replaced by a histidine (H). 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
0.78
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0088
.;.;.;T
Eigen
Benign
0.038
Eigen_PC
Benign
-0.048
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.91
D;.;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.51
.;N;N;.
REVEL
Benign
0.20
Sift
Benign
0.44
.;T;T;.
Sift4G
Benign
0.24
T;T;T;T
Vest4
0.72
MVP
0.28
MPC
1.1
ClinPred
0.30
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.037
gMVP
0.84

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: rs753400378; hg19: chr8-98788331; API