Variant 1-40271844-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.628-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,598,900 control chromosomes in the GnomAD database, including 779,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74279 hom., cov: 32)

Exomes 𝑓: 0.99 ( 704998 hom. )

Consequence

ZMPSTE24
NM_005857.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.228

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=-0.93).

BP6

Variant 1-40271844-T-G is Benign according to our data. Variant chr1-40271844-T-G is described in ClinVar as [Benign]. Clinvar id is 140535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40271844-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ZMPSTE24	NM_005857.5 linkuse as main transcript	c.628-50T>G	intron_variant	ENST00000372759.4
ZMPSTE24	XM_047427582.1 linkuse as main transcript	c.379-50T>G	intron_variant
ZMPSTE24	XM_047427590.1 linkuse as main transcript	c.628-50T>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ZMPSTE24	ENST00000372759.4 linkuse as main transcript	c.628-50T>G	intron_variant	1	NM_005857.5	P1
ZMPSTE24	ENST00000674703.1 linkuse as main transcript	c.*469-50T>G	intron_variant, NMD_transcript_variant
ZMPSTE24	ENST00000675754.1 linkuse as main transcript	c.*370-50T>G	intron_variant, NMD_transcript_variant
ZMPSTE24	ENST00000675937.1 linkuse as main transcript	c.628-50T>G	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.987

AC:

150287

AN:

152192

Hom.:

74221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.982

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

0.924

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.990

Gnomad FIN

AF:

0.958

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.988

GnomAD3 exomes

AF:

0.985

AC:

242837

AN:

246500

Hom.:

119649

AF XY:

0.985

AC XY:

131413

AN XY:

133456

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.930

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.986

Gnomad FIN exome

AF:

0.959

Gnomad NFE exome

AF:

0.987

Gnomad OTH exome

AF:

0.984

GnomAD4 exome

AF:

0.987

AC:

1428075

AN:

1446590

Hom.:

704998

Cov.:

AF XY:

0.987

AC XY:

710899

AN XY:

720344

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

0.929

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.985

Gnomad4 FIN exome

AF:

0.961

Gnomad4 NFE exome

AF:

0.989

Gnomad4 OTH exome

AF:

0.985

GnomAD4 genome

AF:

0.987

AC:

150404

AN:

152310

Hom.:

74279

Cov.:

AF XY:

0.986

AC XY:

73483

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.996

Gnomad4 ASJ

AF:

0.924

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.990

Gnomad4 FIN

AF:

0.958

Gnomad4 NFE

AF:

0.986

Gnomad4 OTH

AF:

0.988

Alfa

AF:

0.972

Hom.:

8307

Bravo

AF:

0.991

Asia WGS

AF:

0.994

AC:

3450

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	literature only	ZMPSTE24 homepage - Leiden Muscular Dystrophy pages	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2018	- -

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

-0.93

CADD

Benign

1.3

DANN

Benign

0.76

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