NM_006762.3:c.458G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006762.3(LAPTM5):​c.458G>C​(p.Ser153Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,936 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: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LAPTM5
NM_006762.3 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
Genes affected
LAPTM5 (HGNC:29612): (lysosomal protein transmembrane 5) This gene encodes a transmembrane receptor that is associated with lysosomes. The encoded protein, also known as E3 protein, may play a role in hematopoiesis. [provided by RefSeq, Feb 2009]
MIR4420 (HGNC:41772): (microRNA 4420) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAPTM5NM_006762.3 linkc.458G>C p.Ser153Thr missense_variant Exon 5 of 8 ENST00000294507.4 NP_006753.1 Q13571Q5TBB8
LAPTM5XM_011542098.3 linkc.287G>C p.Ser96Thr missense_variant Exon 3 of 6 XP_011540400.1
MIR4420NR_039616.1 linkn.*164G>C downstream_gene_variant
MIR4420unassigned_transcript_62 n.*166G>C downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAPTM5ENST00000294507.4 linkc.458G>C p.Ser153Thr missense_variant Exon 5 of 8 1 NM_006762.3 ENSP00000294507.3 Q13571
LAPTM5ENST00000464569.1 linkn.683G>C non_coding_transcript_exon_variant Exon 5 of 8 5
MIR4420ENST00000583944.1 linkn.*164G>C downstream_gene_variant 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455936
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
723634
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.458G>C (p.S153T) alteration is located in exon 5 (coding exon 5) of the LAPTM5 gene. This alteration results from a G to C substitution at nucleotide position 458, causing the serine (S) at amino acid position 153 to be replaced by a threonine (T). 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
Uncertain
0.50
BayesDel_addAF
Benign
0.0094
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.29
Sift
Uncertain
0.0040
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.56
MutPred
0.83
Gain of catalytic residue at S153 (P = 0.1762);
MVP
0.43
MPC
0.69
ClinPred
0.96
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.49
gMVP
0.62

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: rs1350113042; hg19: chr1-31211839; API