Genetic Variant HPS6:p.Ala15Ser (chr10-102065517-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024747.6(HPS6):c.43G>T(p.Ala15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A15V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HPS6
NM_024747.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

1 publications found

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]

HPS6 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
Hermansky-Pudlak syndrome without pulmonary fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HPS6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028654426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024747.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	NM_024747.6	MANE Select	c.43G>T	p.Ala15Ser	missense	Exon 1 of 1	NP_079023.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	ENST00000299238.7	TSL:6 MANE Select	c.43G>T	p.Ala15Ser	missense	Exon 1 of 1	ENSP00000299238.5	Q86YV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

156466

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1402048

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695588

African (AFR)

AF:

0.00

AC:

AN:

29536

American (AMR)

AF:

0.00

AC:

AN:

39968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24840

East Asian (EAS)

AF:

0.00

AC:

AN:

35634

South Asian (SAS)

AF:

0.00

AC:

AN:

80344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4228

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093830

Other (OTH)

AF:

0.00

AC:

AN:

58290

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.12

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.48

M_CAP

Benign

0.018

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.86

REVEL

Benign

0.067

Sift

Benign

0.70

Sift4G

Benign

0.42

Polyphen

0.015

Vest4

0.050

MutPred

0.12

Gain of phosphorylation at A15 (P = 0.0374)

MVP

0.067

MPC

0.46

ClinPred

0.051

GERP RS

-1.6

PromoterAI

0.087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.045

gMVP

0.25

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over