ENST00000445593.6:c.199C>A

Variant names:

• chr8-97775935-C-A
• ENST00000445593.6:c.199C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000445593.6(LAPTM4B):​c.199C>A​(p.Arg67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,315,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: LAPTM4B ENST00000445593.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14127758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.-75C>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4
LOC124901986	XR_007061020.1	n.-160G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000445593.6	c.199C>A	p.Arg67Ser	missense_variant	Exon 1 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.199C>A	p.Arg67Ser	missense_variant	Exon 1 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000521545	c.-75C>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000517924	c.-75C>A		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1315190 Hom.: 0 Cov.: 35 AF XY: 0.00000154 AC XY: 1 AN XY: 648142

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: 0.00000190

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.27	T;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.60	.;N
REVEL	Benign	0.024
Sift	Uncertain	0.0050	.;D
Sift4G	Benign	0.072	T;T
Vest4		0.12
MVP		0.45
MPC		0.82
ClinPred		0.49	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.12
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-98788163;