Genetic Variant LAPTM4B:p.Gly46Ser (chr8-97775872-G-A) – 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.136G>A(p.Gly46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,346,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

LAPTM4B
ENST00000445593.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330

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:

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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=0.082809955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445593.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	NM_018407.6	MANE Select	c.-138G>A		5_prime_UTR	Exon 1 of 7	NP_060877.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAPTM4B	ENST00000445593.6	TSL:1	c.136G>A	p.Gly46Ser	missense	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1	TSL:1	c.136G>A	p.Gly46Ser	missense	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.-138G>A		5_prime_UTR	Exon 1 of 7	ENSP00000428409.1	Q86VI4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

89476

AF XY:

0.0000196

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000223

AC:

AN:

1346398

Hom.:

Cov.:

AF XY:

0.00000452

AC XY:

AN XY:

664146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27614

American (AMR)

AF:

0.00

AC:

AN:

29898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23792

East Asian (EAS)

AF:

0.0000328

AC:

AN:

30492

South Asian (SAS)

AF:

0.0000266

AC:

AN:

75258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4020

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061790

Other (OTH)

AF:

0.00

AC:

AN:

55846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000134

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.4

(source)

DANN

Uncertain

0.98

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

PhyloP100

-0.033

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.45

REVEL

Benign

0.033

Sift

Benign

0.47

Sift4G

Benign

0.18

Vest4

0.069

MVP

0.11

MPC

0.93

ClinPred

0.16

GERP RS

-0.30

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over