10-102065475-A-T
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_024747.6(HPS6):c.1A>T(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,404,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
HPS6
NM_024747.6 initiator_codon
NM_024747.6 initiator_codon
Scores
5
5
6
Clinical Significance
Conservation
PhyloP100: 1.89
Genes affected
HPS6 (HGNC:18817): (HPS6 biogenesis of lysosomal organelles complex 2 subunit 3) This intronless 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 5 protein. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 6. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 6 pathogenic variants. Next in-frame start position is after 678 CDS bases. Genomic position: 102066152. Lost 0.291 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-102065475-A-T is Pathogenic according to our data. Variant chr10-102065475-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3590152.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPS6 | NM_024747.6 | c.1A>T | p.Met1? | initiator_codon_variant | Exon 1 of 1 | ENST00000299238.7 | NP_079023.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000614 AC: 1AN: 162808Hom.: 0 AF XY: 0.0000109 AC XY: 1AN XY: 92020
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GnomAD4 exome AF: 0.0000185 AC: 26AN: 1404054Hom.: 0 Cov.: 31 AF XY: 0.0000201 AC XY: 14AN XY: 696934
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hermansky-Pudlak syndrome 6 Pathogenic:1
Mar 22, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.1133);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at