1-40258100-A-G

Variant names:

• chr1-40258100-A-G
• rs151221982
• ENST00000674703.1:n.-172A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000674703.1(ZMPSTE24):​n.-172A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000507 in 985,726 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: ZMPSTE24 ENST00000674703.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 0 publications found

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-DT (HGNC:55402): (ZMPSTE24 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMPSTE24	NM_005857.5	c.-172A>G		upstream_gene_variant		ENST00000372759.4	NP_005848.2
ZMPSTE24	XM_047427590.1	c.-172A>G		upstream_gene_variant			XP_047283546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24	ENST00000372759.4	c.-172A>G		upstream_gene_variant		1	NM_005857.5	ENSP00000361845.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000507 AC: 5 AN: 985726 Hom.: 0 Cov.: 13 AF XY: 0.00000402 AC XY: 2 AN XY: 497004

African (AFR) AF: 0.00 AC: 0 AN: 24022

American (AMR) AF: 0.00 AC: 0 AN: 33222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18300

East Asian (EAS) AF: 0.00 AC: 0 AN: 36682

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3002

European-Non Finnish (NFE) AF: 0.00000551 AC: 4 AN: 726454

Other (OTH) AF: 0.00 AC: 0 AN: 43824

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.24
PromoterAI		0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151221982; hg19: chr1-40723772;