8-97816062-G-T

Variant names:

• chr8-97816062-G-T
• rs1386816062
• NM_018407.6:c.290G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018407.6(LAPTM4B):​c.290G>T​(p.Arg97Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LAPTM4B NM_018407.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37908703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.290G>T	p.Arg97Leu	missense_variant	Exon 4 of 7	ENST00000521545.7	NP_060877.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000521545.7	c.290G>T	p.Arg97Leu	missense_variant	Exon 4 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.563G>T	p.Arg188Leu	missense_variant	Exon 4 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.563G>T	p.Arg188Leu	missense_variant	Exon 4 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000517924.5	c.314G>T	p.Arg105Leu	missense_variant	Exon 4 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;.;.;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.95	D;.;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.79	T
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.6	.;D;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0090	.;D;D;.
Sift4G	Uncertain	0.021	D;D;D;T
Vest4		0.60
MVP		0.23
MPC		0.88
ClinPred		1.0	D
GERP RS		-8.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1386816062; hg19: chr8-98828290;