10-102065475-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_024747.6(HPS6):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

HPS6
NM_024747.6 initiator_codon

Scores

5
5
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89
Variant links:
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 6 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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HPS6NM_024747.6 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 1 ENST00000299238.7 NP_079023.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HPS6ENST00000299238.7 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 1 6 NM_024747.6 ENSP00000299238.5 Q86YV9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.29
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Benign
0.25
N
LIST_S2
Uncertain
0.90
D
M_CAP
Pathogenic
0.84
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Benign
-0.56
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.57
MutPred
1.0
Loss of MoRF binding (P = 0.1133);
MVP
0.26
ClinPred
1.0
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.95
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763073715; hg19: chr10-103825232; API