rs200449378
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_181507.2(HPS5):c.285-10A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
HPS5
NM_181507.2 splice_polypyrimidine_tract, intron
NM_181507.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00004705
2
Clinical Significance
Conservation
PhyloP100: -0.168
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 11-18310943-T-A is Benign according to our data. Variant chr11-18310943-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2852011.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS5 | NM_181507.2 | c.285-10A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000349215.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS5 | ENST00000349215.8 | c.285-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_181507.2 | P1 | |||
HPS5 | ENST00000396253.7 | c.-58-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
HPS5 | ENST00000438420.6 | c.-58-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
HPS5 | ENST00000531848.1 | c.-58-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249608Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135002
GnomAD3 exomes
AF:
AC:
2
AN:
249608
Hom.:
AF XY:
AC XY:
2
AN XY:
135002
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461220Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726980
GnomAD4 exome
AF:
AC:
1
AN:
1461220
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726980
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at