Genetic Variant LAPTM4B:p.Leu16Val (chr8-97775782-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000445593.6(LAPTM4B):c.46C>G(p.Leu16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,412,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L16F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

LAPTM4B
ENST00000445593.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130

Publications

0 publications found

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]

LAPTM4B links:

LOC124901986 (HGNC:):

LOC124901986 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07175115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6 link	c.-228C>G		upstream_gene_variant		ENST00000521545.7	NP_060877.4	Q86VI4-2
LOC124901986	XR_007061020.1 link	n.-7G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAPTM4B	ENST00000445593.6 link	c.46C>G	p.Leu16Val	missense_variant	Exon 1 of 7	1		ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1 link	c.46C>G	p.Leu16Val	missense_variant	Exon 1 of 7	1		ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545.7 link	c.-228C>G		upstream_gene_variant		1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000517924.5 link	c.-228C>G		upstream_gene_variant		5		ENSP00000429868.2	H0YBN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000496

AC:

AN:

1412414

Hom.:

Cov.:

AF XY:

0.00000571

AC XY:

AN XY:

700732

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32590

American (AMR)

AF:

0.00

AC:

AN:

40502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25324

East Asian (EAS)

AF:

0.00

AC:

AN:

37718

South Asian (SAS)

AF:

0.00

AC:

AN:

83548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4828

European-Non Finnish (NFE)

AF:

0.00000549

AC:

AN:

1093166

Other (OTH)

AF:

0.00

AC:

AN:

58670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.8

(source)

DANN

Benign

0.95

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.22

T;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.1

PhyloP100

0.13

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.070

.;N

REVEL

Benign

0.034

Sift

Benign

0.19

.;T

Sift4G

Benign

1.0

T;T

Vest4

0.082

MVP

0.22

MPC

0.29

ClinPred

0.12

GERP RS

-1.2

PromoterAI

0.11

Neutral

(source)

Varity_R

0.045

gMVP

0.018

Mutation Taster

=299/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr8-97775782-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over