rs763676668

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024747.6(HPS6):​c.1255G>A​(p.Ala419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HPS6
NM_024747.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.809
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05927813).
BP6
Variant 10-102066729-G-A is Benign according to our data. Variant chr10-102066729-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435462.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HPS6NM_024747.6 linkuse as main transcriptc.1255G>A p.Ala419Thr 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.1255G>A p.Ala419Thr missense_variant 1/16 NM_024747.6 ENSP00000299238.5 Q86YV9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250826
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.0000621
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461628
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJan 26, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
14
DANN
Benign
0.87
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.72
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.070
N
REVEL
Benign
0.11
Sift
Benign
0.82
T
Sift4G
Benign
0.42
T
Polyphen
0.0010
B
Vest4
0.066
MutPred
0.12
Gain of glycosylation at A419 (P = 0.0678);
MVP
0.52
MPC
0.48
ClinPred
0.011
T
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.026
gMVP
0.12

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: rs763676668; hg19: chr10-103826486; COSMIC: COSV105160081; API