Genetic Variant ZMPSTE24-DT:n.93C>A (chr1-40257902-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000567508.3(ZMPSTE24-DT):n.93C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 254,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

ZMPSTE24-DT
ENST00000567508.3 non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.0720

Publications

0 publications found

Variant links:

Genes affected

ZMPSTE24-DT (HGNC:55402): (ZMPSTE24 divergent transcript)

ZMPSTE24-DT links:

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZMPSTE24-DT	ENST00000567508.3 link	n.93C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
ZMPSTE24	ENST00000674703.1 link	n.-370G>T	upstream_gene_variant			ENSP00000501674.1	A0A6Q8PF67
ZMPSTE24	ENST00000675937.1 link	n.-370G>T	upstream_gene_variant			ENSP00000502683.1	A0A6Q8PHG9

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.000390

AC:

AN:

102656

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

AN XY:

55272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3640

American (AMR)

AF:

0.00119

AC:

AN:

5044

Ashkenazi Jewish (ASJ)

AF:

0.000737

AC:

AN:

2712

East Asian (EAS)

AF:

0.00

AC:

AN:

4954

South Asian (SAS)

AF:

0.0000578

AC:

AN:

17294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

400

European-Non Finnish (NFE)

AF:

0.000446

AC:

AN:

58310

Other (OTH)

AF:

0.000907

AC:

AN:

5514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000617

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41586

American (AMR)

AF:

0.00209

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68032

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000491

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

ZMPSTE24 homepage - Leiden Muscular Dystrophy pages

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

(source)

DANN

Benign

0.61

PhyloP100

-0.072

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr1-40257902-G-T

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