8-97775937-C-CGGCGGGCTCCAGGCGAGGCGGGCTCCAGGCGA

Position:

• chr8-97775937-C-CGGCGGGCTCCAGGCGAGGCGGGCTCCAGGCGA

Variant summary

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

The ENST00000445593.6(LAPTM4B):​c.222_223insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG​(p.Ser75AlafsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,451,714 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: LAPTM4B ENST00000445593.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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/exons	MANE	UniProt
LAPTM4B	NM_018407.6	c.-52_-51insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG		5_prime_UTR_variant	1/7	ENST00000521545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAPTM4B	ENST00000445593.6	c.222_223insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG	p.Ser75AlafsTer15	frameshift_variant	1/7	1
LAPTM4B	ENST00000619747.1	c.222_223insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG	p.Ser75AlafsTer15	frameshift_variant	1/7	1
LAPTM4B	ENST00000521545.7	c.-52_-51insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG		5_prime_UTR_variant	1/7	1	NM_018407.6	P1
LAPTM4B	ENST00000517924.5	c.-52_-51insGCTCCAGGCGAGGCGGGCTCCAGGCGAGGCGG		5_prime_UTR_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 23 AN: 151808 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000316 AC: 2 AN: 63330 Hom.: 0 AF XY: 0.0000547 AC XY: 2 AN XY: 36534

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000760

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 133 AN: 1299796 Hom.: 0 Cov.: 35 AF XY: 0.000106 AC XY: 68 AN XY: 638880

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: 0.0000152

Gnomad4 FIN exome AF: 0.0000267

Gnomad4 NFE exome AF: 0.000118

Gnomad4 OTH exome AF: 0.0000929

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151918 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74258

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764278197; hg19: chr8-98788165;