8-97819170-A-T

Variant names:

• chr8-97819170-A-T
• rs538196230
• NM_018407.6:c.439A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018407.6(LAPTM4B):​c.439A>T​(p.Met147Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M147V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAPTM4B NM_018407.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 0 publications found

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]

ACMG classification

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=0.26039618).

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.439A>T	p.Met147Leu	missense	Exon 5 of 7	NP_060877.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.439A>T	p.Met147Leu	missense	Exon 5 of 7	ENSP00000428409.1	Q86VI4-2
	LAPTM4B	ENST00000445593.6	TSL:1	c.712A>T	p.Met238Leu	missense	Exon 5 of 7	ENSP00000402301.2	Q86VI4-3
	LAPTM4B	ENST00000619747.1	TSL:1	c.712A>T	p.Met238Leu	missense	Exon 5 of 7	ENSP00000482533.1	Q86VI4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000618 AC: 9 AN: 1457172 Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3 AN XY: 725148

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109682

Other (OTH) AF: 0.00 AC: 0 AN: 60146

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.85
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Vest4		0.53
MVP		0.26
MPC		0.29
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.20
gMVP		0.75
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs538196230; hg19: chr8-98831398;