rs1816908189

Variant names:

• chr8-97816072-G-A
• NM_018407.6:c.300G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-97816072-G-A
• chr8-97816072-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018407.6(LAPTM4B):​c.300G>A​(p.Trp100*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAPTM4B NM_018407.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.300G>A	p.Trp100*	stop_gained	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.300G>A	p.Trp100*	stop_gained	Exon 4 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.573G>A	p.Trp191*	stop_gained	Exon 4 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.573G>A	p.Trp191*	stop_gained	Exon 4 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000517924.5	c.324G>A	p.Trp108*	stop_gained	Exon 4 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460600 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	51
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
Vest4		0.90
ClinPred		1.0	D
GERP RS		5.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.51		Position offset: 25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-98828300;