dbSNP rs959939906: LAPTM4B:p.Arg67Ser (chr8-97775935-C-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 NM_018407.6(LAPTM4B):c.-75C>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 0.00000152 in 1,315,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

LAPTM4B
NM_018407.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.309

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=0.14127758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6 link	c.-75C>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4	Q86VI4-2
LOC124901986	XR_007061020.1 link	n.-160G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAPTM4B	ENST00000445593.6 link	c.199C>A	p.Arg67Ser	missense_variant	Exon 1 of 7	1		ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1 link	c.199C>A	p.Arg67Ser	missense_variant	Exon 1 of 7	1		ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545.7 link	c.-75C>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000517924.5 link	c.-75C>A		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000429868.2	H0YBN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1315190

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

648142

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26738

American (AMR)

AF:

0.00

AC:

AN:

22536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21884

East Asian (EAS)

AF:

0.00

AC:

AN:

28850

South Asian (SAS)

AF:

0.00

AC:

AN:

68470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4016

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1049982

Other (OTH)

AF:

0.00

AC:

AN:

54428

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.27

T;.

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

PhyloP100

0.31

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.60

.;N

REVEL

Benign

0.024

Sift

Uncertain

0.0050

.;D

Sift4G

Benign

0.072

T;T

Vest4

0.12

MVP

0.45

MPC

0.82

ClinPred

0.49

GERP RS

2.2

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.12

gMVP

0.28

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

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rs959939906

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