Variant rs188058932 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_005857.5(ZMPSTE24):c.1059+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,445,246 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 13 hom. )

Consequence

ZMPSTE24
NM_005857.5 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.207

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00158 (241/152188) while in subpopulation NFE AF= 0.00212 (144/68010). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5 linkuse as main transcript	c.1059+61G>A		intron_variant		ENST00000372759.4	NP_005848.2	O75844
ZMPSTE24	XM_047427582.1 linkuse as main transcript	c.810+61G>A		intron_variant			XP_047283538.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ZMPSTE24	ENST00000372759.4 linkuse as main transcript	c.1059+61G>A	intron_variant	1	NM_005857.5	ENSP00000361845.3	O75844
ZMPSTE24	ENST00000674703.1 linkuse as main transcript	n.*900+61G>A	intron_variant			ENSP00000501674.1	A0A6Q8PF67
ZMPSTE24	ENST00000675754.1 linkuse as main transcript	n.*801+61G>A	intron_variant			ENSP00000502555.1	A0A6Q8PH40
ZMPSTE24	ENST00000675937.1 linkuse as main transcript	n.*304+61G>A	intron_variant			ENSP00000502683.1	A0A6Q8PHG9

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00228

AC:

2953

AN:

1293058

Hom.:

AF XY:

0.00230

AC XY:

1496

AN XY:

649624

show subpopulations

Gnomad4 AFR exome

AF:

0.000169

Gnomad4 AMR exome

AF:

0.000571

Gnomad4 ASJ exome

AF:

0.000243

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.00381

Gnomad4 NFE exome

AF:

0.00262

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152188

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00156

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

ZMPSTE24 homepage - Leiden Muscular Dystrophy pages

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.72

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