11-18320534-T-C

Variant names:

• chr11-18320534-T-C
• rs10741741
• NM_181507.2:c.-50+1412A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181507.2(HPS5):​c.-50+1412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,084 control chromosomes in the GnomAD database, including 29,135 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (29135 hom., cov: 33)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 15 publications found

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]

HPS5 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 5

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181507.2. 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
	HPS5	NM_181507.2	MANE Select	c.-50+1412A>G		intron	N/A	NP_852608.1	Q9UPZ3-1
	HPS5	NM_001440902.1		c.-50+1412A>G		intron	N/A	NP_001427831.1
	HPS5	NM_001440903.1		c.-50+1543A>G		intron	N/A	NP_001427832.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS5	ENST00000349215.8	TSL:1 MANE Select	c.-50+1412A>G		intron	N/A	ENSP00000265967.5	Q9UPZ3-1
	HPS5	ENST00000396253.7	TSL:1	c.-235+1412A>G		intron	N/A	ENSP00000379552.3	Q9UPZ3-2
	HPS5	ENST00000438420.6	TSL:1	c.-235+1599A>G		intron	N/A	ENSP00000399590.2	Q9UPZ3-2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91135 AN: 151964 Hom.: 29131 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 91173 AN: 152084 Hom.: 29135 Cov.: 33 AF XY: 0.605 AC XY: 45013 AN XY: 74348

African (AFR) AF: 0.383 AC: 15898 AN: 41472

American (AMR) AF: 0.679 AC: 10373 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1903 AN: 3468

East Asian (EAS) AF: 0.965 AC: 4999 AN: 5182

South Asian (SAS) AF: 0.661 AC: 3191 AN: 4826

European-Finnish (FIN) AF: 0.700 AC: 7403 AN: 10576

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45334 AN: 67964

Other (OTH) AF: 0.597 AC: 1263 AN: 2114

Alfa AF: 0.636 Hom.: 76039

Bravo AF: 0.593

Asia WGS AF: 0.798 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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: rs10741741; hg19: chr11-18342081;