NM_000195.5:c.*1215C>T

Variant names:

• chr10-98416349-G-A
• rs3830024
• NM_000195.5:c.*1215C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000195.5(HPS1):​c.*1215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,080 control chromosomes in the GnomAD database, including 10,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10408 hom., cov: 33)
  • Exomes 𝑓: 0.30 (6 hom.)
• Consequence: HPS1 NM_000195.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.116
• Publications: 8 publications found

Genes affected

HPS1 (HGNC:5163): (HPS1 biogenesis of lysosomal organelles complex 3 subunit 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is a component of three different protein complexes termed biogenesis of lysosome-related organelles complex (BLOC)-3, BLOC4, and BLOC5. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 1. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on chromosome 22. [provided by RefSeq, Aug 2015]

HPS1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Hermansky-Pudlak syndrome with pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289758 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-98416349-G-A is Benign according to our data. Variant chr10-98416349-G-A is described in ClinVar as Benign. ClinVar VariationId is 298310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000195.5. 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
	HPS1	NM_000195.5	MANE Select	c.*1215C>T		3_prime_UTR	Exon 20 of 20	NP_000186.2
	HPS1	NM_001322476.2		c.*1215C>T		3_prime_UTR	Exon 20 of 20	NP_001309405.1	Q92902-1
	HPS1	NM_001322477.2		c.*1215C>T		3_prime_UTR	Exon 20 of 20	NP_001309406.1	Q92902-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS1	ENST00000361490.9	TSL:1 MANE Select	c.*1215C>T		3_prime_UTR	Exon 20 of 20	ENSP00000355310.4	Q92902-1
	ENSG00000289758	ENST00000699159.1		n.*1487-593C>T		intron	N/A	ENSP00000514167.1	A0A8V8TP71
	HPS1	ENST00000699134.1		c.*1215C>T		3_prime_UTR	Exon 19 of 19	ENSP00000514151.1	A0A8V8TPJ1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53015 AN: 151814 Hom.: 10395 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.297 AC: 44 AN: 148 Hom.: 6 Cov.: 0 AF XY: 0.333 AC XY: 28 AN XY: 84

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.301 AC: 41 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.349 AC: 53076 AN: 151932 Hom.: 10408 Cov.: 33 AF XY: 0.350 AC XY: 25976 AN XY: 74288

African (AFR) AF: 0.527 AC: 21804 AN: 41370

American (AMR) AF: 0.342 AC: 5235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2125 AN: 5140

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4816

European-Finnish (FIN) AF: 0.204 AC: 2158 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17147 AN: 67964

Other (OTH) AF: 0.318 AC: 671 AN: 2108

Alfa AF: 0.302 Hom.: 937

Bravo AF: 0.362

Asia WGS AF: 0.451 AC: 1565 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hermansky-Pudlak syndrome 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.29
PhyloP100		-0.12
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: rs3830024; hg19: chr10-100176106; COSMIC: COSV105206668; COSMIC: COSV105206668;