rs148450315

Variant names:

• chr10-98422414-C-G
• rs148450315
• NM_000195.5:c.1698G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-98422414-C-G
• chr10-98422414-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000195.5(HPS1):​c.1698G>C​(p.Ser566Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S566S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HPS1 NM_000195.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 0 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Hermansky-Pudlak syndrome with pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289758 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 10-98422414-C-G is Benign according to our data. Variant chr10-98422414-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1995359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.67 with no splicing effect.

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.1698G>C	p.Ser566Ser	synonymous	Exon 17 of 20	NP_000186.2
	HPS1	NM_001322476.2		c.1698G>C	p.Ser566Ser	synonymous	Exon 17 of 20	NP_001309405.1	Q92902-1
	HPS1	NM_001322477.2		c.1698G>C	p.Ser566Ser	synonymous	Exon 17 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.1698G>C	p.Ser566Ser	synonymous	Exon 17 of 20	ENSP00000355310.4	Q92902-1
	HPS1	ENST00000467246.5	TSL:1	n.*1057G>C		non_coding_transcript_exon	Exon 16 of 19	ENSP00000514163.1	A0A8V8TP71
	ENSG00000289758	ENST00000699159.1		n.*1057G>C		non_coding_transcript_exon	Exon 16 of 24	ENSP00000514167.1	A0A8V8TP71

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.058
DANN	Benign	0.41
PhyloP100		-1.7

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: rs148450315; hg19: chr10-100182171;