rs16827109

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005857.5(ZMPSTE24):c.627+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 1,613,024 control chromosomes in the GnomAD database, including 8,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 716 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7523 hom. )

Consequence

ZMPSTE24
NM_005857.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.241

Publications

9 publications found

Variant links:

Genes affected

ZMPSTE24 (HGNC:12877): (zinc metallopeptidase STE24) This gene encodes a member of the peptidase M48A family. The encoded protein is a zinc metalloproteinase involved in the two step post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A to form mature lamin A. Mutations in this gene have been associated with mandibuloacral dysplasia and restrictive dermopathy. [provided by RefSeq, Jul 2008]

ZMPSTE24 Gene-Disease associations (from GenCC):

lethal restrictive dermopathy
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet
mandibuloacral dysplasia with type B lipodystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
restrictive dermopathy 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Hutchinson-Gilford progeria syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ZMPSTE24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-40270145-T-G is Benign according to our data. Variant chr1-40270145-T-G is described in ClinVar as [Benign]. Clinvar id is 140531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5 link	c.627+18T>G	intron_variant	Intron 5 of 9	ENST00000372759.4	NP_005848.2	O75844
ZMPSTE24	XM_047427582.1 link	c.378+18T>G	intron_variant	Intron 4 of 8		XP_047283538.1
ZMPSTE24	XM_047427590.1 link	c.627+18T>G	intron_variant	Intron 5 of 6		XP_047283546.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZMPSTE24	ENST00000372759.4 link	c.627+18T>G	intron_variant	Intron 5 of 9	1	NM_005857.5	ENSP00000361845.3	O75844
ZMPSTE24	ENST00000674703.1 link	n.*468+18T>G	intron_variant	Intron 6 of 10			ENSP00000501674.1	A0A6Q8PF67
ZMPSTE24	ENST00000675754.1 link	n.*369+18T>G	intron_variant	Intron 6 of 10			ENSP00000502555.1	A0A6Q8PH40
ZMPSTE24	ENST00000675937.1 link	n.627+18T>G	intron_variant	Intron 5 of 10			ENSP00000502683.1	A0A6Q8PHG9

Frequencies

GnomAD3 genomes

AF:

0.0901

AC:

13718

AN:

152170

Hom.:

714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0647

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0884

Gnomad OTH

AF:

0.0833

GnomAD2 exomes

AF:

0.107

AC:

26839

AN:

251184

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.0635

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0894

Gnomad NFE exome

AF:

0.0892

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0990

AC:

144638

AN:

1460736

Hom.:

7523

Cov.:

AF XY:

0.0995

AC XY:

72322

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.0616

AC:

2059

AN:

33450

American (AMR)

AF:

0.140

AC:

6238

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0598

AC:

1561

AN:

26110

East Asian (EAS)

AF:

0.132

AC:

5220

AN:

39592

South Asian (SAS)

AF:

0.147

AC:

12658

AN:

86214

European-Finnish (FIN)

AF:

0.0899

AC:

4790

AN:

53302

Middle Eastern (MID)

AF:

0.0685

AC:

394

AN:

5748

European-Non Finnish (NFE)

AF:

0.0952

AC:

105750

AN:

1111292

Other (OTH)

AF:

0.0989

AC:

5968

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6105

12209

18314

24418

30523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0902

AC:

13738

AN:

152288

Hom.:

716

Cov.:

AF XY:

0.0923

AC XY:

6874

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0645

AC:

2683

AN:

41572

American (AMR)

AF:

0.136

AC:

2081

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

791

AN:

5182

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4830

European-Finnish (FIN)

AF:

0.0925

AC:

981

AN:

10604

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0884

AC:

6014

AN:

68018

Other (OTH)

AF:

0.0866

AC:

183

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

624

1248

1871

2495

3119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0897

Hom.:

951

Bravo

AF:

0.0918

Asia WGS

AF:

0.131

AC:

456

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ZMPSTE24 homepage - Leiden Muscular Dystrophy pages

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 04, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.0

(source)

DANN

Benign

0.78

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs16827109

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over