rs118204100
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000190.4(HMBS):c.593G>A(p.Trp198*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HMBS
NM_000190.4 stop_gained
NM_000190.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.89
Publications
20 publications found
Genes affected
HMBS (HGNC:4982): (hydroxymethylbilane synthase) This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
HMBS Gene-Disease associations (from GenCC):
- acute intermittent porphyriaInheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 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 11-119091507-G-A is Pathogenic according to our data. Variant chr11-119091507-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1453.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1398832Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 689970
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1398832
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
689970
African (AFR)
AF:
AC:
0
AN:
31588
American (AMR)
AF:
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25176
East Asian (EAS)
AF:
AC:
0
AN:
35738
South Asian (SAS)
AF:
AC:
0
AN:
79232
European-Finnish (FIN)
AF:
AC:
0
AN:
49214
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1078508
Other (OTH)
AF:
AC:
0
AN:
57976
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ExAC
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Acute intermittent porphyria Pathogenic:1
Dec 01, 1991
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
0.95, 0.88, 0.88, 0.82, 0.95
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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