Variant 1-40270145-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr1-40270145-T-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5 linkuse as main transcript	c.627+18T>G	intron_variant	ENST00000372759.4	NP_005848.2	O75844
ZMPSTE24	XM_047427582.1 linkuse as main transcript	c.378+18T>G	intron_variant		XP_047283538.1
ZMPSTE24	XM_047427590.1 linkuse as main transcript	c.627+18T>G	intron_variant		XP_047283546.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ZMPSTE24	ENST00000372759.4 linkuse as main transcript	c.627+18T>G	intron_variant	1	NM_005857.5	ENSP00000361845.3	O75844
ZMPSTE24	ENST00000674703.1 linkuse as main transcript	n.*468+18T>G	intron_variant			ENSP00000501674.1	A0A6Q8PF67
ZMPSTE24	ENST00000675754.1 linkuse as main transcript	n.*369+18T>G	intron_variant			ENSP00000502555.1	A0A6Q8PH40
ZMPSTE24	ENST00000675937.1 linkuse as main transcript	n.627+18T>G	intron_variant			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

GnomAD3 exomes

AF:

0.107

AC:

26839

AN:

251184

Hom.:

1622

AF XY:

0.108

AC XY:

14600

AN XY:

135776

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 SAS exome

AF:

0.147

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

Gnomad4 AFR exome

AF:

0.0616

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.0598

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0899

Gnomad4 NFE exome

AF:

0.0952

Gnomad4 OTH exome

AF:

0.0989

GnomAD4 genome

AF:

0.0902

AC:

13738

AN:

152288

Hom.:

716

Cov.:

AF XY:

0.0923

AC XY:

6874

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0645

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.0925

Gnomad4 NFE

AF:

0.0884

Gnomad4 OTH

AF:

0.0866

Alfa

AF:

0.0878

Hom.:

623

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2019	- -
not provided, no classification provided	literature only	ZMPSTE24 homepage - Leiden Muscular Dystrophy pages	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.0

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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