10-102066106-G-T

Variant names:

• chr10-102066106-G-T
• rs200584437
• NM_024747.6:c.632G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024747.6(HPS6):​c.632G>T​(p.Gly211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G211A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HPS6 NM_024747.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 6 publications found

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, G2P, Labcorp Genetics (formerly Invitae)
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	NM_024747.6	MANE Select	c.632G>T	p.Gly211Val	missense	Exon 1 of 1	NP_079023.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	ENST00000299238.7	TSL:6 MANE Select	c.632G>T	p.Gly211Val	missense	Exon 1 of 1	ENSP00000299238.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.036	D
Sift4G	Benign	0.13	T
Polyphen		0.92	P
Vest4		0.52
MutPred		0.41		Gain of catalytic residue at G211 (P = 0.1174)
MVP		0.34
MPC		1.5
ClinPred		0.84	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.53
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs200584437; hg19: chr10-103825863;