2-20035049-T-G

Variant names:

• chr2-20035049-T-G
• rs759307681
• NM_014713.5:c.446A>C

Variant summary

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

The NM_014713.5(LAPTM4A):​c.446A>C​(p.Tyr149Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Y149C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• 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>C	p.Tyr149Ser	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>C	p.Tyr149Ser	missense_variant	Exon 5 of 7	1	NM_014713.5	ENSP00000175091.4
LAPTM4A	ENST00000483117.1	n.195A>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248762 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134514

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: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.60		Gain of disorder (P = 0.0017);
MVP		0.30
MPC		0.39
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs759307681; hg19: chr2-20234810;