rs7122032

chr11-18306101-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181507.2(HPS5):c.824+34A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,434,014 control chromosomes in the GnomAD database, including 9,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1585 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8319 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.309

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This 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 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-18306101-T-G is Benign according to our data. Variant chr11-18306101-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS5	NM_181507.2	c.824+34A>C		intron_variant		ENST00000349215.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS5	ENST00000349215.8	c.824+34A>C		intron_variant		1	NM_181507.2	P1
HPS5	ENST00000396253.7	c.482+34A>C		intron_variant		1
HPS5	ENST00000438420.6	c.482+34A>C		intron_variant		1
HPS5	ENST00000531848.1	c.482+34A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21213 AN: 152072 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.137 AC: 34279 AN: 250790 Hom.: 2741 AF XY: 0.131 AC XY: 17820 AN XY: 135580

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.107 AC: 136957 AN: 1281824 Hom.: 8319 Cov.: 19 AF XY: 0.107 AC XY: 69336 AN XY: 647048

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0922

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.139 AC: 21227 AN: 152190 Hom.: 1585 Cov.: 32 AF XY: 0.142 AC XY: 10603 AN XY: 74422

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.150

Alfa AF: 0.123 Hom.: 239

Bravo AF: 0.140

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.7
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

Other links and lift over

dbSNP: rs7122032; hg19: chr11-18327648;