rs759307681

Variant names:

• chr2-20035049-T-A
• NM_014713.5:c.446A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-20035049-T-A
• chr2-20035049-T-C
• chr2-20035049-T-G

Variant summary

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

The NM_014713.5(LAPTM4A):​c.446A>T​(p.Tyr149Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,982 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: 6.9e-7 (0 hom.)
• Consequence: LAPTM4A NM_014713.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

Genes affected

LAPTM4A (HGNC:6924): (lysosomal protein transmembrane 4 alpha) This gene encodes a protein that has four predicted transmembrane domains. The function of this gene has not yet been determined; however, studies in the mouse homolog suggest a role in the transport of small molecules across endosomal and lysosomal membranes. [provided by RefSeq, Jul 2008]

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
LAPTM4A	NM_014713.5	c.446A>T	p.Tyr149Phe	missense_variant	Exon 5 of 7	ENST00000175091.5	NP_055528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4A	ENST00000175091.5	c.446A>T	p.Tyr149Phe	missense_variant	Exon 5 of 7	1	NM_014713.5	ENSP00000175091.4
LAPTM4A	ENST00000483117.1	n.195A>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458982 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.31
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.64		Gain of methylation at K150 (P = 0.0252);
MVP		0.26
MPC		0.63
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr2-20234810;