1-92262862-C-CTTGA
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_053274.3(GLMN):c.1470_1473dupTCAA(p.Thr492fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GLMN
NM_053274.3 frameshift, splice_region
NM_053274.3 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.296
Publications
1 publications found
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]
GLMN Gene-Disease associations (from GenCC):
- glomuvenous malformationInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 1-92262862-C-CTTGA is Pathogenic according to our data. Variant chr1-92262862-C-CTTGA is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3779702.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_053274.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GLMN | MANE Select | c.1470_1473dupTCAA | p.Thr492fs | frameshift splice_region | Exon 16 of 19 | NP_444504.1 | Q92990-1 | ||
| GLMN | c.1428_1431dupTCAA | p.Thr478fs | frameshift splice_region | Exon 15 of 18 | NP_001306612.1 | B4DJ85 | |||
| GLMN | n.1478_1481dupTCAA | splice_region non_coding_transcript_exon | Exon 15 of 18 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GLMN | TSL:1 MANE Select | c.1470_1473dupTCAA | p.Thr492fs | frameshift splice_region | Exon 16 of 19 | ENSP00000359385.3 | Q92990-1 | ||
| GLMN | TSL:1 | n.*131_*134dupTCAA | splice_region non_coding_transcript_exon | Exon 15 of 18 | ENSP00000436829.1 | Q92990-2 | |||
| GLMN | TSL:1 | n.*131_*134dupTCAA | 3_prime_UTR | Exon 15 of 18 | ENSP00000436829.1 | Q92990-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152200
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD2 exomes AF: 0.00000404 AC: 1AN: 247624 AF XY: 0.00000747 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
247624
AF XY:
Gnomad AFR exome
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Gnomad OTH exome
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 942974Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0AN XY: 487482
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
942974
Hom.:
Cov.:
13
AF XY:
AC XY:
0
AN XY:
487482
African (AFR)
AF:
AC:
0
AN:
24246
American (AMR)
AF:
AC:
0
AN:
42696
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22136
East Asian (EAS)
AF:
AC:
0
AN:
36464
South Asian (SAS)
AF:
AC:
0
AN:
75868
European-Finnish (FIN)
AF:
AC:
0
AN:
50478
Middle Eastern (MID)
AF:
AC:
0
AN:
4684
European-Non Finnish (NFE)
AF:
AC:
0
AN:
644018
Other (OTH)
AF:
AC:
0
AN:
42384
GnomAD4 genome 0.00000657 AC: 1AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74488 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152318
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74488
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41570
American (AMR)
AF:
AC:
0
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
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0
1
1
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0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
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ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Glomuvenous malformation (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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