rs753928208
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_181507.2(HPS5):c.3096_3098delCCT(p.Leu1033del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000124 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L1032L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
HPS5
NM_181507.2 disruptive_inframe_deletion
NM_181507.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.79
Publications
2 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
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_181507.2. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 11-18282180-AAGG-A is Pathogenic according to our data. Variant chr11-18282180-AAGG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 427877.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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | MANE Select | c.3096_3098delCCT | p.Leu1033del | disruptive_inframe_deletion | Exon 22 of 23 | NP_852608.1 | Q9UPZ3-1 | ||
| HPS5 | c.3096_3098delCCT | p.Leu1033del | disruptive_inframe_deletion | Exon 22 of 24 | NP_001427831.1 | ||||
| HPS5 | c.3096_3098delCCT | p.Leu1033del | disruptive_inframe_deletion | Exon 22 of 24 | NP_001427832.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | TSL:1 MANE Select | c.3096_3098delCCT | p.Leu1033del | disruptive_inframe_deletion | Exon 22 of 23 | ENSP00000265967.5 | Q9UPZ3-1 | ||
| HPS5 | TSL:1 | c.2754_2756delCCT | p.Leu919del | disruptive_inframe_deletion | Exon 21 of 22 | ENSP00000379552.3 | Q9UPZ3-2 | ||
| HPS5 | TSL:1 | c.2754_2756delCCT | p.Leu919del | disruptive_inframe_deletion | Exon 21 of 22 | ENSP00000399590.2 | Q9UPZ3-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152158
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727244 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461882
Hom.:
AF XY:
AC XY:
1
AN XY:
727244
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:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112004
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152158
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74352
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2092
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
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar 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
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