8-97775857-G-A

Variant names:

Variant summary

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

The NM_018407.6(LAPTM4B):c.-153G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,528,720 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

LAPTM4B
NM_018407.6 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.897

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=0.08204183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6 link	c.-153G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4	Q86VI4-2
LOC124901986	XR_007061020.1 link	n.-82C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAPTM4B	ENST00000445593.6 link	c.121G>A	p.Gly41Ser	missense_variant	Exon 1 of 7	1		ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1 link	c.121G>A	p.Gly41Ser	missense_variant	Exon 1 of 7	1		ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545.7 link	c.-153G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000517924.5 link	c.-153G>A		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000429868.2	H0YBN1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1376598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679568

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30064

American (AMR)

AF:

0.00

AC:

AN:

34698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24706

East Asian (EAS)

AF:

0.00

AC:

AN:

34028

South Asian (SAS)

AF:

0.00

AC:

AN:

78754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074928

Other (OTH)

AF:

0.00

AC:

AN:

57326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.121G>A (p.G41S) alteration is located in exon 1 (coding exon 1) of the LAPTM4B gene. This alteration results from a G to A substitution at nucleotide position 121, causing the glycine (G) at amino acid position 41 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.9

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.50

T;.

M_CAP

Benign

0.056

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.90

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.22

.;N

REVEL

Benign

0.034

Sift

Benign

0.077

.;T

Sift4G

Benign

0.27

T;T

Vest4

0.088

MVP

0.076

MPC

0.93

ClinPred

0.30

GERP RS

-4.4

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.11

Mutation Taster

=300/0

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.

8-97775857-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over