Genetic Variant LAPTM4B:p.Ala23Pro (chr8-97775803-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000445593.6(LAPTM4B):c.67G>C(p.Ala23Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LAPTM4B
ENST00000445593.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10941526).

BP6

Variant 8-97775803-G-C is Benign according to our data. Variant chr8-97775803-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3290105.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-207G>C		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.67G>C	p.Ala23Pro	missense	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1	TSL:1	c.67G>C	p.Ala23Pro	missense	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.-207G>C		5_prime_UTR	Exon 1 of 7	ENSP00000428409.1	Q86VI4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000141

AC:

AN:

1420836

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32814

American (AMR)

AF:

0.00

AC:

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25508

East Asian (EAS)

AF:

0.00

AC:

AN:

38086

South Asian (SAS)

AF:

0.00

AC:

AN:

83434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4640

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1098456

Other (OTH)

AF:

0.00

AC:

AN:

59052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.4

(source)

DANN

Benign

0.96

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.28

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

0.16

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.61

REVEL

Benign

0.20

Sift

Benign

0.18

Sift4G

Benign

0.36

Vest4

0.10

MVP

0.12

MPC

0.43

ClinPred

0.056

GERP RS

-2.1

PromoterAI

-0.24

Neutral

(source)

Varity_R

0.066

gMVP

0.024

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over