3-149162442-CAG-C

Position:

• chr3-149162442-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032383.5(HPS3):​c.2292+111_2292+112delGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,047,440 control chromosomes in the GnomAD database, including 10,883 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2558 hom., cov: 29)
  • Exomes 𝑓: 0.13 (8325 hom.)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.121

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]

CP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-149162442-CAG-C is Benign according to our data. Variant chr3-149162442-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1268637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5	c.2292+111_2292+112delGA		intron_variant		ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.2292+111_2292+112delGA		intron_variant		1	NM_032383.5	ENSP00000296051.2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25965 AN: 151958 Hom.: 2555 Cov.: 29

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.132 AC: 22370 AN: 169590 Hom.: 1670 AF XY: 0.130 AC XY: 11962 AN XY: 92062

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.0806

Gnomad SAS exome AF: 0.0969

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.131 AC: 117201 AN: 895364 Hom.: 8325 AF XY: 0.129 AC XY: 59860 AN XY: 464852

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0987

Gnomad4 SAS exome AF: 0.0989

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.171 AC: 25972 AN: 152076 Hom.: 2558 Cov.: 29 AF XY: 0.169 AC XY: 12577 AN XY: 74330

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.155

Alfa AF: 0.153 Hom.: 365

Bravo AF: 0.176

Asia WGS AF: 0.104 AC: 362 AN: 3478

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

GeneDx

Jul 09, 2018

- -

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: rs58796831; hg19: chr3-148880229;