19-11575039-T-G

Variant names:

• chr19-11575039-T-G
• rs1599630500
• NM_001611.5:c.949A>C

Variant summary

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

The NM_001611.5(ACP5):​c.949A>C​(p.Thr317Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACP5 NM_001611.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904638 (HGNC:):

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
ACP5	NM_001611.5	c.949A>C	p.Thr317Pro	missense_variant	Exon 5 of 5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1	c.949A>C	p.Thr317Pro	missense_variant	Exon 5 of 5		NM_001611.5	ENSP00000496973.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;D;D;D
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	.;.;.;.;T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.69	D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.8	M;M;M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	.;N;N;.;N
REVEL	Uncertain	0.60
Sift	Uncertain	0.012	.;D;D;.;D
Sift4G	Uncertain	0.014	.;D;D;D;D
Polyphen		0.99	D;D;D;D;D
Vest4		0.42, 0.43, 0.43
MutPred		0.51		Loss of phosphorylation at T317 (P = 0.0354);Loss of phosphorylation at T317 (P = 0.0354);Loss of phosphorylation at T317 (P = 0.0354);Loss of phosphorylation at T317 (P = 0.0354);Loss of phosphorylation at T317 (P = 0.0354);
MVP		0.80
MPC		1.1
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.73
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

LitVar

Other links and lift over

dbSNP: rs1599630500; hg19: chr19-11685854;