rs1131692151
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_181507.2(HPS5):c.2750_2751delAG(p.Glu917ValfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
HPS5
NM_181507.2 frameshift
NM_181507.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.76
Publications
1 publications found
Genes affected
HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
HPS5 Gene-Disease associations (from GenCC):
- Hermansky-Pudlak syndrome 5Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
- Hermansky-Pudlak syndrome without pulmonary fibrosisInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
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 11-18286676-ACT-A is Pathogenic according to our data. Variant chr11-18286676-ACT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 427883.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_181507.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | NM_181507.2 | MANE Select | c.2750_2751delAG | p.Glu917ValfsTer14 | frameshift | Exon 19 of 23 | NP_852608.1 | ||
| HPS5 | NM_001440902.1 | c.2750_2751delAG | p.Glu917ValfsTer14 | frameshift | Exon 19 of 24 | NP_001427831.1 | |||
| HPS5 | NM_001440903.1 | c.2750_2751delAG | p.Glu917ValfsTer14 | frameshift | Exon 19 of 24 | NP_001427832.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | ENST00000349215.8 | TSL:1 MANE Select | c.2750_2751delAG | p.Glu917ValfsTer14 | frameshift | Exon 19 of 23 | ENSP00000265967.5 | ||
| HPS5 | ENST00000396253.7 | TSL:1 | c.2408_2409delAG | p.Glu803ValfsTer14 | frameshift | Exon 18 of 22 | ENSP00000379552.3 | ||
| HPS5 | ENST00000438420.6 | TSL:1 | c.2408_2409delAG | p.Glu803ValfsTer14 | frameshift | Exon 18 of 22 | ENSP00000399590.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461814Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727212 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461814
Hom.:
AF XY:
AC XY:
2
AN XY:
727212
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111940
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Hermansky-Pudlak syndrome 5 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.