rs397710976

chr3-149167992-AT-Achr3-149167992-AT-ATTchr3-149167992-AT-ATTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_032383.5(HPS3):c.2887+19del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,278,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-149167992-AT-A is Benign according to our data. Variant chr3-149167992-AT-A is described in ClinVar as [Benign]. Clinvar id is 774850.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-149167992-AT-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00234 (2636/1128202) while in subpopulation MID AF= 0.00288 (14/4864). AF 95% confidence interval is 0.0027. There are 0 homozygotes in gnomad4_exome. There are 1210 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS3	NM_032383.5	c.2887+19del		intron_variant		ENST00000296051.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS3	ENST00000296051.7	c.2887+19del		intron_variant		1	NM_032383.5	P1

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150268 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00234 AC: 2636 AN: 1128202 Hom.: 0 Cov.: 18 AF XY: 0.00211 AC XY: 1210 AN XY: 572546

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.000867

Gnomad4 ASJ exome AF: 0.00146

Gnomad4 EAS exome AF: 0.000685

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.000280

Gnomad4 NFE exome AF: 0.00279

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150268 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00955 Hom.: 479

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs397710976; hg19: chr3-148885779;