chr8-97815336-A-C

Variant names:

• chr8-97815336-A-C
• NM_018407.6:c.220A>C

Variant summary

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

The NM_018407.6(LAPTM4B):​c.220A>C​(p.Ile74Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAPTM4B NM_018407.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.66

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.220A>C	p.Ile74Leu	missense_variant	Exon 3 of 7	ENST00000521545.7	NP_060877.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000521545.7	c.220A>C	p.Ile74Leu	missense_variant	Exon 3 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.493A>C	p.Ile165Leu	missense_variant	Exon 3 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.493A>C	p.Ile165Leu	missense_variant	Exon 3 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000517924.5	c.244A>C	p.Ile82Leu	missense_variant	Exon 3 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461578 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727132

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: 8.99e-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
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;.;.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.79	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	.;N;N;.
REVEL	Benign	0.26
Sift	Uncertain	0.022	.;D;D;.
Sift4G	Uncertain	0.017	D;D;D;T
Vest4		0.81
MVP		0.53
MPC		0.30
ClinPred		0.93	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.86

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: chr8-98827564;