Variant 22-26451986-ACGCG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_022081.6(HPS4):c.*1243_*1246del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.11 ( 875 hom., cov: 0)

Exomes 𝑓: 0.037 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

HPS4
NM_022081.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.278

Variant links:

Genes affected

HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

HPS4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS4	NM_022081.6 linkuse as main transcript	c.1243_1246del		3_prime_UTR_variant	14/14	ENST00000398145.7	NP_071364.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS4	ENST00000398145.7 linkuse as main transcript	c.1243_1246del		3_prime_UTR_variant	14/14	1	NM_022081.6	ENSP00000381213	P2	Q9NQG7-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

14380

AN:

134224

Hom.:

875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0864

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.128

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0372

AC:

529

AN:

14232

Hom.:

AF XY:

0.0387

AC XY:

312

AN XY:

8052

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.0292

Gnomad4 ASJ exome

AF:

0.0673

Gnomad4 EAS exome

AF:

0.0625

Gnomad4 SAS exome

AF:

0.0378

Gnomad4 FIN exome

AF:

0.0522

Gnomad4 NFE exome

AF:

0.0359

Gnomad4 OTH exome

AF:

0.0411

GnomAD4 genome

AF:

0.107

AC:

14389

AN:

134302

Hom.:

875

Cov.:

AF XY:

0.107

AC XY:

6945

AN XY:

64832

show subpopulations

Gnomad4 AFR

AF:

0.0866

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.0989

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.126

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hermansky-Pudlak syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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