chr11-18285367-G-GTC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_181507.2(HPS5):c.2928_2929dupGA(p.Thr977ArgfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T977T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HPS5
NM_181507.2 frameshift
NM_181507.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0280
Publications
3 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, ClinGen, Labcorp Genetics (formerly Invitae)
- 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 18 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 11-18285367-G-GTC is Pathogenic according to our data. Variant chr11-18285367-G-GTC is described in ClinVar as Pathogenic. ClinVar VariationId is 21820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | MANE Select | c.2928_2929dupGA | p.Thr977ArgfsTer15 | frameshift | Exon 20 of 23 | NP_852608.1 | Q9UPZ3-1 | ||
| HPS5 | c.2928_2929dupGA | p.Thr977ArgfsTer15 | frameshift | Exon 20 of 24 | NP_001427831.1 | ||||
| HPS5 | c.2928_2929dupGA | p.Thr977ArgfsTer15 | frameshift | Exon 20 of 24 | NP_001427832.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | TSL:1 MANE Select | c.2928_2929dupGA | p.Thr977ArgfsTer15 | frameshift | Exon 20 of 23 | ENSP00000265967.5 | Q9UPZ3-1 | ||
| HPS5 | TSL:1 | c.2586_2587dupGA | p.Thr863ArgfsTer15 | frameshift | Exon 19 of 22 | ENSP00000379552.3 | Q9UPZ3-2 | ||
| HPS5 | TSL:1 | c.2586_2587dupGA | p.Thr863ArgfsTer15 | frameshift | Exon 19 of 22 | ENSP00000399590.2 | Q9UPZ3-2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1AN: 1458498Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725780 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1458498
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
725780
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33396
American (AMR)
AF:
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26110
East Asian (EAS)
AF:
AC:
0
AN:
39620
South Asian (SAS)
AF:
AC:
0
AN:
86200
European-Finnish (FIN)
AF:
AC:
0
AN:
53296
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1109138
Other (OTH)
AF:
AC:
0
AN:
60276
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Hermansky-Pudlak syndrome 5 (2)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
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.