chr10-102065518-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024747.6(HPS6):ā€‹c.44C>Gā€‹(p.Ala15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000784 in 1,402,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000078 ( 0 hom. )

Consequence

HPS6
NM_024747.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046513647).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HPS6NM_024747.6 linkuse as main transcriptc.44C>G p.Ala15Gly missense_variant 1/1 ENST00000299238.7 NP_079023.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HPS6ENST00000299238.7 linkuse as main transcriptc.44C>G p.Ala15Gly missense_variant 1/1 NM_024747.6 ENSP00000299238 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000632
AC:
1
AN:
158346
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
89394
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000143
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000784
AC:
11
AN:
1402484
Hom.:
0
Cov.:
31
AF XY:
0.0000101
AC XY:
7
AN XY:
695822
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000113
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 06, 2023The c.44C>G (p.A15G) alteration is located in exon 1 (coding exon 1) of the HPS6 gene. This alteration results from a C to G substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
20
DANN
Benign
0.95
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.047
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.092
Sift
Benign
0.38
T
Sift4G
Benign
0.29
T
Polyphen
0.0060
B
Vest4
0.080
MutPred
0.19
Loss of helix (P = 0.028);
MVP
0.088
MPC
0.49
ClinPred
0.095
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.052
gMVP
0.26

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: rs764430976; hg19: chr10-103825275; API