1-40276227-C-T

Position:

• chr1-40276227-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005857.5(ZMPSTE24):​c.769+4192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,274 control chromosomes in the GnomAD database, including 62,467 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 0.90 (62467 hom., cov: 32)
• Consequence: ZMPSTE24 NM_005857.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5	c.769+4192C>T		intron_variant		ENST00000372759.4	NP_005848.2
ZMPSTE24	XM_047427582.1	c.520+4192C>T		intron_variant			XP_047283538.1
ZMPSTE24	XM_047427590.1	c.770-3893C>T		intron_variant			XP_047283546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24	ENST00000372759.4	c.769+4192C>T		intron_variant		1	NM_005857.5	ENSP00000361845.3
ZMPSTE24	ENST00000674703.1	n.*610+4192C>T		intron_variant				ENSP00000501674.1
ZMPSTE24	ENST00000675754.1	n.*511+4192C>T		intron_variant				ENSP00000502555.1
ZMPSTE24	ENST00000675937.1	n.770-3893C>T		intron_variant				ENSP00000502683.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137625 AN: 152156 Hom.: 62401 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.884

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.905 AC: 137750 AN: 152274 Hom.: 62467 Cov.: 32 AF XY: 0.905 AC XY: 67361 AN XY: 74456

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.885

Alfa AF: 0.879 Hom.: 82059

Bravo AF: 0.910

Asia WGS AF: 0.887 AC: 3085 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

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	-0.98
CADD	Benign	3.3
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs6676644; hg19: chr1-40741899;