Genetic Variant LAPTM4B:p.Tyr32His (chr8-97776103-T-C) – 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 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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:

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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=0.2329551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018407.6. 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.94T>C	p.Tyr32His	missense	Exon 1 of 7	NP_060877.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.94T>C	p.Tyr32His	missense	Exon 1 of 7	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000445593.6	TSL:1	c.367T>C	p.Tyr123His	missense	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1	TSL:1	c.367T>C	p.Tyr123His	missense	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197960

AF XY:

0.00000898

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1424858

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29892

American (AMR)

AF:

0.0000704

AC:

AN:

42614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35342

South Asian (SAS)

AF:

0.00

AC:

AN:

84360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4938

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101034

Other (OTH)

AF:

0.00

AC:

AN:

59150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000839

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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0088

Eigen

Benign

0.038

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

PhyloP100

3.3

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.51

REVEL

Benign

0.20

Sift

Benign

0.44

Sift4G

Benign

0.24

Vest4

0.72

MVP

0.28

MPC

1.1

ClinPred

0.30

GERP RS

1.6

PromoterAI

-0.096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.84

Mutation Taster

=64/36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over