chr1-40271844-T-G
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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
NM_005857.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.228
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]
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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 | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZMPSTE24 | NM_005857.5 | c.628-50T>G | intron_variant | ENST00000372759.4 | NP_005848.2 | |||
ZMPSTE24 | XM_047427582.1 | c.379-50T>G | intron_variant | XP_047283538.1 | ||||
ZMPSTE24 | XM_047427590.1 | c.628-50T>G | intron_variant | XP_047283546.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZMPSTE24 | ENST00000372759.4 | c.628-50T>G | intron_variant | 1 | NM_005857.5 | ENSP00000361845.3 | ||||
ZMPSTE24 | ENST00000674703.1 | n.*469-50T>G | intron_variant | ENSP00000501674.1 | ||||||
ZMPSTE24 | ENST00000675754.1 | n.*370-50T>G | intron_variant | ENSP00000502555.1 | ||||||
ZMPSTE24 | ENST00000675937.1 | n.628-50T>G | intron_variant | ENSP00000502683.1 |
Frequencies
GnomAD3 genomes AF: 0.987 AC: 150287AN: 152192Hom.: 74221 Cov.: 32
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GnomAD3 exomes AF: 0.985 AC: 242837AN: 246500Hom.: 119649 AF XY: 0.985 AC XY: 131413AN XY: 133456
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GnomAD4 exome AF: 0.987 AC: 1428075AN: 1446590Hom.: 704998 Cov.: 25 AF XY: 0.987 AC XY: 710899AN XY: 720344
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GnomAD4 genome AF: 0.987 AC: 150404AN: 152310Hom.: 74279 Cov.: 32 AF XY: 0.986 AC XY: 73483AN XY: 74492
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2Other:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at