NM_001611.5:c.598G>A

Variant names:

• chr19-11576380-C-T
• rs2229531
• NM_001611.5:c.598G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001611.5(ACP5):​c.598G>A​(p.Val200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,610,798 control chromosomes in the GnomAD database, including 10,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (734 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9374 hom.)
• Consequence: ACP5 NM_001611.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.03
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00640592).
• BP6: Variant 19-11576380-C-T is Benign according to our data. Variant chr19-11576380-C-T is described in ClinVar as Benign. ClinVar VariationId is 257479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001611.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP5	NM_001611.5	MANE Select	c.598G>A	p.Val200Met	missense	Exon 4 of 5	NP_001602.1
	ACP5	NM_001111034.3		c.598G>A	p.Val200Met	missense	Exon 5 of 6	NP_001104504.1
	ACP5	NM_001111035.3		c.598G>A	p.Val200Met	missense	Exon 6 of 7	NP_001104505.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP5	ENST00000648477.1	MANE Select	c.598G>A	p.Val200Met	missense	Exon 4 of 5	ENSP00000496973.1
	ACP5	ENST00000218758.10	TSL:1	c.598G>A	p.Val200Met	missense	Exon 6 of 7	ENSP00000218758.4
	ACP5	ENST00000412435.7	TSL:2	c.598G>A	p.Val200Met	missense	Exon 5 of 6	ENSP00000392374.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13346 AN: 152102 Hom.: 733 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0971 AC: 24160 AN: 248768 AF XY: 0.101

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.0613

Gnomad ASJ exome AF: 0.0885

Gnomad EAS exome AF: 0.0839

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.111 AC: 161535 AN: 1458576 Hom.: 9374 Cov.: 34 AF XY: 0.111 AC XY: 80313 AN XY: 725064

African (AFR) AF: 0.0254 AC: 850 AN: 33410

American (AMR) AF: 0.0647 AC: 2892 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 2345 AN: 26108

East Asian (EAS) AF: 0.0823 AC: 3258 AN: 39604

South Asian (SAS) AF: 0.0954 AC: 8219 AN: 86170

European-Finnish (FIN) AF: 0.134 AC: 7042 AN: 52570

Middle Eastern (MID) AF: 0.145 AC: 813 AN: 5614

European-Non Finnish (NFE) AF: 0.117 AC: 129603 AN: 1110222

Other (OTH) AF: 0.108 AC: 6513 AN: 60210

GnomAD4 genome AF: 0.0877 AC: 13345 AN: 152222 Hom.: 734 Cov.: 32 AF XY: 0.0871 AC XY: 6479 AN XY: 74418

African (AFR) AF: 0.0280 AC: 1162 AN: 41566

American (AMR) AF: 0.0755 AC: 1154 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3468

East Asian (EAS) AF: 0.0846 AC: 438 AN: 5176

South Asian (SAS) AF: 0.0876 AC: 422 AN: 4816

European-Finnish (FIN) AF: 0.137 AC: 1448 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7984 AN: 67996

Other (OTH) AF: 0.105 AC: 222 AN: 2108

Alfa AF: 0.109 Hom.: 4120

Bravo AF: 0.0812

TwinsUK AF: 0.114 AC: 421

ALSPAC AF: 0.109 AC: 421

ESP6500AA AF: 0.0286 AC: 126

ESP6500EA AF: 0.110 AC: 942

ExAC AF: 0.0952 AC: 11554

Asia WGS AF: 0.0860 AC: 298 AN: 3478

EpiCase AF: 0.119

EpiControl AF: 0.121

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported.

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Spondyloenchondrodysplasia with immune dysregulation Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	0.0070
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.44	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.10
MPC		0.86
ClinPred		0.039	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.62
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229531; hg19: chr19-11687195; COSMIC: COSV54535670; COSMIC: COSV54535670;