Variant 19-11575133-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001611.5(ACP5):c.855T>C(p.Thr285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,614,192 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 275 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 220 hom. )

Consequence

ACP5
NM_001611.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.98

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:

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=0.0017488003).

BP6

Variant 19-11575133-A-G is Benign according to our data. Variant chr19-11575133-A-G is described in ClinVar as [Benign]. Clinvar id is 464892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP5	NM_001611.5 linkuse as main transcript	c.855T>C	p.Thr285=	synonymous_variant	5/5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1 linkuse as main transcript	c.855T>C	p.Thr285=	synonymous_variant	5/5		NM_001611.5	ENSP00000496973	P3

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4909

AN:

152188

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00848

AC:

2132

AN:

251458

Hom.:

AF XY:

0.00633

AC XY:

860

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.00674

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00328

AC:

4800

AN:

1461886

Hom.:

220

Cov.:

AF XY:

0.00283

AC XY:

2059

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.00695

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00743

GnomAD4 genome

AF:

0.0322

AC:

4911

AN:

152306

Hom.:

275

Cov.:

AF XY:

0.0309

AC XY:

2300

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0371

ESP6500AA

AF:

0.108

AC:

478

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0105

AC:

1271

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.021

DANN

Benign

0.37

FATHMM_MKL

Benign

0.0062

MetaRNN

Benign

0.0017

MutationTaster

Benign

1.0

N;N;N;N;N

Vest4

0.17

GERP RS

-1.6

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