rs199580546

Variant names:

• chr19-11576719-C-A
• NM_001611.5:c.386G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-11576719-C-A
• chr19-11576719-C-G
• chr19-11576719-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001611.5(ACP5):​c.386G>T​(p.Arg129Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ACP5 NM_001611.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP5	NM_001611.5	c.386G>T	p.Arg129Leu	missense_variant	Exon 3 of 5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1	c.386G>T	p.Arg129Leu	missense_variant	Exon 3 of 5		NM_001611.5	ENSP00000496973.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.386G>T (p.R129L) alteration is located in exon 5 (coding exon 2) of the ACP5 gene. This alteration results from a G to T substitution at nucleotide position 386, causing the arginine (R) at amino acid position 129 to be replaced by a leucine (L). 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D;D;D;D;D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	.;.;.;.;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	3.2	M;M;M;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.2	.;D;D;.;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0060	.;D;D;.;D
Sift4G	Uncertain	0.0050	.;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.84, 0.84, 0.84
MutPred		0.68		Loss of MoRF binding (P = 0.0318);Loss of MoRF binding (P = 0.0318);Loss of MoRF binding (P = 0.0318);Loss of MoRF binding (P = 0.0318);Loss of MoRF binding (P = 0.0318);
MVP		0.83
MPC		1.1
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.89
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11687534;