rs78985808

Positions:

• chr1-40281212-T-A
• chr1-40281212-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005857.5(ZMPSTE24):​c.770-131T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 928,578 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ZMPSTE24 NM_005857.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5	c.770-131T>A		intron_variant		ENST00000372759.4	NP_005848.2
ZMPSTE24	XM_047427590.1	c.*914T>A		3_prime_UTR_variant	7/7		XP_047283546.1
ZMPSTE24	XM_047427582.1	c.521-131T>A		intron_variant			XP_047283538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24	ENST00000372759.4	c.770-131T>A		intron_variant		1	NM_005857.5	ENSP00000361845	P1
ZMPSTE24	ENST00000674703.1	c.*611-131T>A		intron_variant, NMD_transcript_variant				ENSP00000501674
ZMPSTE24	ENST00000675754.1	c.*512-131T>A		intron_variant, NMD_transcript_variant				ENSP00000502555
ZMPSTE24	ENST00000675937.1	c.*15-131T>A		intron_variant, NMD_transcript_variant				ENSP00000502683

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 10 AN: 776334 Hom.: 0 AF XY: 0.00000983 AC XY: 4 AN XY: 406746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000127

Gnomad4 NFE exome AF: 0.00000191

Gnomad4 OTH exome AF: 0.000107

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.50

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: rs78985808; hg19: chr1-40746884;