8-97775872-G-T

Variant names:

• chr8-97775872-G-T
• rs754567791
• NM_018407.6:c.-138G>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.-138G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,346,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: LAPTM4B NM_018407.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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]

LOC124901986 (HGNC:):

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=0.16179088).

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.-138G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_060877.4
	LAPTM4B	NM_018407.6	MANE Select	c.-138G>T		5_prime_UTR	Exon 1 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.-138G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000428409.1	Q86VI4-2
	LAPTM4B	ENST00000445593.6	TSL:1	c.136G>T	p.Gly46Cys	missense	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
	LAPTM4B	ENST00000619747.1	TSL:1	c.136G>T	p.Gly46Cys	missense	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 89476 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1346398 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 664146

African (AFR) AF: 0.00 AC: 0 AN: 27614

American (AMR) AF: 0.00 AC: 0 AN: 29898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23792

East Asian (EAS) AF: 0.0000984 AC: 3 AN: 30492

South Asian (SAS) AF: 0.00 AC: 0 AN: 75258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061790

Other (OTH) AF: 0.00 AC: 0 AN: 55846

GnomAD4 genome Cov.: 33

Alfa AF: 0.000326 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.7
DANN	Uncertain	0.98
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.033
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.057
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Vest4		0.21
MVP		0.39
MPC		1.0
ClinPred		0.24	T
GERP RS		-0.30
PromoterAI		-0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.14
Mutation Taster		=99/1	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: rs754567791; hg19: chr8-98788100;