3-132332238-T-C

Variant names:

• chr3-132332238-T-C
• rs1937412778
• NM_001099.5:c.350T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001099.5(ACP3):​c.350T>C​(p.Met117Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACP3 NM_001099.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP3	NM_001099.5	c.350T>C	p.Met117Thr	missense_variant	Exon 4 of 10	ENST00000336375.10	NP_001090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP3	ENST00000336375.10	c.350T>C	p.Met117Thr	missense_variant	Exon 4 of 10	1	NM_001099.5	ENSP00000337471.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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.: 32

Bravo AF: 0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350T>C (p.M117T) alteration is located in exon 4 (coding exon 4) of the ACPP gene. This alteration results from a T to C substitution at nucleotide position 350, causing the methionine (M) at amino acid position 117 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;.;M;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.021	D;D;D;T
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.98	D;.;.;D
Vest4		0.47
MutPred		0.76		Gain of glycosylation at M117 (P = 0.0143);.;Gain of glycosylation at M117 (P = 0.0143);Gain of glycosylation at M117 (P = 0.0143);
MVP		0.19
MPC		0.50
ClinPred		0.89	D
GERP RS		6.0
Varity_R		0.60
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1937412778; hg19: chr3-132051082;