chr22-26451986-A-ACG

Variant names:

• chr22-26451986-A-ACG
• rs10573454
• NM_022081.6:c.*1245_*1246dupCG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_022081.6(HPS4):​c.*1245_*1246dupCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: HPS4 NM_022081.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

Genes affected

HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000304 (41/134834) while in subpopulation SAS AF= 0.000985 (4/4062). AF 95% confidence interval is 0.000576. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS4	NM_022081.6	c.*1245_*1246dupCG		3_prime_UTR_variant	Exon 14 of 14	ENST00000398145.7	NP_071364.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS4	ENST00000398145	c.*1245_*1246dupCG		3_prime_UTR_variant	Exon 14 of 14	1	NM_022081.6	ENSP00000381213.2

Frequencies

GnomAD3 genomes AF: 0.000304 AC: 41 AN: 134754 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000664

Gnomad SAS AF: 0.000984

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000775

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000279 AC: 4 AN: 14342 Hom.: 0 Cov.: 0 AF XY: 0.000370 AC XY: 3 AN XY: 8110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000304 AC: 41 AN: 134834 Hom.: 0 Cov.: 0 AF XY: 0.000307 AC XY: 20 AN XY: 65094

Gnomad4 AFR AF: 0.000816

Gnomad4 AMR AF: 0.000148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000665

Gnomad4 SAS AF: 0.000985

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000775

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000268

ClinVar

Not reported in ClinVar

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: rs10573454; hg19: chr22-26847952;