8-97775926-C-T

Variant names:

• chr8-97775926-C-T
• rs760702744
• ENST00000445593.6:c.190C>T

Variant summary

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

The ENST00000445593.6(LAPTM4B):​c.190C>T​(p.Gln64*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,045,298 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: 0.0000019 (0 hom.)
• Consequence: LAPTM4B ENST00000445593.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

LOC124901986 (HGNC:):

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.-84C>T		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4
LOC124901986	XR_007061020.1	n.-151G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000445593.6	c.190C>T	p.Gln64*	stop_gained	Exon 1 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.190C>T	p.Gln64*	stop_gained	Exon 1 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000521545	c.-84C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000517924	c.-84C>T		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000184 AC: 1 AN: 54450 Hom.: 0 AF XY: 0.0000314 AC XY: 1 AN XY: 31804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1045298 Hom.: 0 Cov.: 33 AF XY: 0.00000387 AC XY: 2 AN XY: 516306

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: 0.0000179

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000122

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	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	0.071
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.11	N
Vest4		0.32
GERP RS		3.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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

LitVar

Other links and lift over

dbSNP: rs760702744; hg19: chr8-98788154;