rs6600323

Positions:

• chr1-40278055-G-A

Variant summary

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

The NM_005857.5(ZMPSTE24):​c.770-3288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 150,756 control chromosomes in the GnomAD database, including 21,916 homozygotes. 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 0.52 (21916 hom., cov: 28)
• Consequence: ZMPSTE24 NM_005857.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMPSTE24	NM_005857.5	c.770-3288G>A		intron_variant		ENST00000372759.4
ZMPSTE24	XM_047427582.1	c.521-3288G>A		intron_variant
ZMPSTE24	XM_047427590.1	c.770-2065G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMPSTE24	ENST00000372759.4	c.770-3288G>A		intron_variant		1	NM_005857.5	P1
ZMPSTE24	ENST00000674703.1	c.*611-3288G>A		intron_variant, NMD_transcript_variant
ZMPSTE24	ENST00000675754.1	c.*512-3288G>A		intron_variant, NMD_transcript_variant
ZMPSTE24	ENST00000675937.1	c.770-2065G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.522 AC: 78660 AN: 150646 Hom.: 21875 Cov.: 28

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.522 AC: 78763 AN: 150756 Hom.: 21916 Cov.: 28 AF XY: 0.525 AC XY: 38626 AN XY: 73566

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.480

Alfa AF: 0.433 Hom.: 24463

Bravo AF: 0.532

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.13

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: rs6600323; hg19: chr1-40743727; COSMIC: COSV65638967;