chr3-149167992-A-ATT

Position:

• chr3-149167992-A-ATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_032383.5(HPS3):​c.2887+18_2887+19dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 0)
  • Exomes 𝑓: 0.010 (18 hom.)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.188

Genes affected

HPS3 (HGNC:15597): (HPS3 biogenesis of lysosomal organelles complex 2 subunit 1) This gene encodes a protein containing a potential clathrin-binding motif, consensus dileucine signals, and tyrosine-based sorting signals for targeting to vesicles of lysosomal lineage. The encoded protein may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 3. [provided by RefSeq, Apr 2015]

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

HPS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-149167992-A-ATT is Benign according to our data. Variant chr3-149167992-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1169104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00695 (1045/150398) while in subpopulation SAS AF= 0.0198 (95/4788). AF 95% confidence interval is 0.0166. There are 8 homozygotes in gnomad4. There are 540 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5	c.2887+18_2887+19dupTT		intron_variant		ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.2887+18_2887+19dupTT		intron_variant		1	NM_032383.5	ENSP00000296051.2

Frequencies

GnomAD3 genomes AF: 0.00695 AC: 1045 AN: 150284 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0200

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00966

Gnomad OTH AF: 0.00388

GnomAD4 exome AF: 0.0101 AC: 11520 AN: 1137512 Hom.: 18 Cov.: 18 AF XY: 0.0105 AC XY: 6037 AN XY: 577410

Gnomad4 AFR exome AF: 0.00763

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00577

Gnomad4 EAS exome AF: 0.000678

Gnomad4 SAS exome AF: 0.0185

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.00934

GnomAD4 genome AF: 0.00695 AC: 1045 AN: 150398 Hom.: 8 Cov.: 0 AF XY: 0.00736 AC XY: 540 AN XY: 73418

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00186

Gnomad4 ASJ AF: 0.00378

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0198

Gnomad4 FIN AF: 0.0168

Gnomad4 NFE AF: 0.00966

Gnomad4 OTH AF: 0.00384

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hermansky-Pudlak syndrome Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 27, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397710976; hg19: chr3-148885779;