Variant 10-102067980-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024747.6(HPS6):c.*178T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 707,136 control chromosomes in the GnomAD database, including 19,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3647 hom., cov: 32)

Exomes 𝑓: 0.22 ( 16024 hom. )

Consequence

HPS6
NM_024747.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.514

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-102067980-T-G is Benign according to our data. Variant chr10-102067980-T-G is described in ClinVar as [Benign]. Clinvar id is 261761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS6	NM_024747.6 linkuse as main transcript	c.*178T>G		3_prime_UTR_variant	1/1	ENST00000299238.7	NP_079023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS6	ENST00000299238.7 linkuse as main transcript	c.*178T>G		3_prime_UTR_variant	1/1		NM_024747.6	ENSP00000299238	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31418

AN:

152044

Hom.:

3639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.218

AC:

120848

AN:

554974

Hom.:

16024

Cov.:

AF XY:

0.221

AC XY:

65413

AN XY:

296478

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.207

AC:

31448

AN:

152162

Hom.:

3647

Cov.:

AF XY:

0.209

AC XY:

15534

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.195

Hom.:

5614

Bravo

AF:

0.216

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hermansky-Pudlak syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over