chr1-92263655-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_053274.3(GLMN):​c.1376del​(p.Gly459ValfsTer17) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

GLMN
NM_053274.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.62
Variant links:
Genes affected
GLMN (HGNC:14373): (glomulin, FKBP associated protein) This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutations in this gene have been associated with glomuvenous malformations, also called glomangiomas. Multiple splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-92263655-AC-A is Pathogenic according to our data. Variant chr1-92263655-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 1323020.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLMNNM_053274.3 linkuse as main transcriptc.1376del p.Gly459ValfsTer17 frameshift_variant 15/19 ENST00000370360.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLMNENST00000370360.8 linkuse as main transcriptc.1376del p.Gly459ValfsTer17 frameshift_variant 15/191 NM_053274.3 P1Q92990-1
GLMNENST00000495106.5 linkuse as main transcriptc.*37del 3_prime_UTR_variant, NMD_transcript_variant 14/181 Q92990-2
GLMNENST00000495852.6 linkuse as main transcriptc.599del p.Gly200ValfsTer17 frameshift_variant 7/105
GLMNENST00000463560.1 linkuse as main transcriptc.639del p.Gly214ValfsTer17 frameshift_variant 8/95

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Glomuvenous malformation Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingRevvity Omics, RevvityFeb 24, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-92729212; API