dbSNP rs147115345: ACP5:p.Asp287Asp (chr19-11575127-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001611.5(ACP5):c.861C>T(p.Asp287Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,614,234 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 19 hom. )

Consequence

ACP5
NM_001611.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.567

Variant links:

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]

ACP5 links:

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]

ZNF627 links:

LOC124904638 (HGNC:):

LOC124904638 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004789263).

BP6

Variant 19-11575127-G-A is Benign according to our data. Variant chr19-11575127-G-A is described in ClinVar as [Benign]. Clinvar id is 533475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.567 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00158 (240/152352) while in subpopulation SAS AF= 0.0106 (51/4826). AF 95% confidence interval is 0.00826. There are 3 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP5	NM_001611.5 link	c.861C>T	p.Asp287Asp	synonymous_variant	Exon 5 of 5	ENST00000648477.1	NP_001602.1	P13686A0A024R7F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1 link	c.861C>T	p.Asp287Asp	synonymous_variant	Exon 5 of 5		NM_001611.5	ENSP00000496973.1		P13686

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00248

AC:

623

AN:

251456

Hom.:

AF XY:

0.00316

AC XY:

430

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00157

AC:

2288

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1454

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.000879

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152352

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00149

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00267

AC:

324

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

DANN

Benign

0.55

FATHMM_MKL

Benign

0.084

MetaRNN

Benign

0.0048

Vest4

0.18

MVP

0.67

GERP RS

2.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over