NM_001099.5:c.496G>T

Variant names:

• chr3-132337495-G-T
• rs930064679
• NM_001099.5:c.496G>T

Variant summary

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

The NM_001099.5(ACP3):​c.496G>T​(p.Glu166*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACP3 NM_001099.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

Genes affected

ACP3 (HGNC:125): (acid phosphatase 3) This gene encodes an enzyme that catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is synthesized under androgen regulation and is secreted by the epithelial cells of the prostate gland. An alternatively spliced transcript variant encoding a longer isoform has been found for this gene. This isoform contains a transmembrane domain and is localized in the plasma membrane-endosomal-lysosomal pathway. [provided by RefSeq, Sep 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
ACP3	NM_001099.5	c.496G>T	p.Glu166*	stop_gained	Exon 5 of 10	ENST00000336375.10	NP_001090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP3	ENST00000336375.10	c.496G>T	p.Glu166*	stop_gained	Exon 5 of 10	1	NM_001099.5	ENSP00000337471.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.80	D
Vest4		0.92
GERP RS		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs930064679; hg19: chr3-132056339; COSMIC: COSV100313208; COSMIC: COSV100313208;