rs2074981

Variant names:

• chr19-38381695-C-A
• rs2074981
• NM_002812.5:c.804-422C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002812.5(PSMD8):​c.804-422C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,242 control chromosomes in the GnomAD database, including 1,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1360 hom., cov: 32)
• Consequence: PSMD8 NM_002812.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 12 publications found

Genes affected

PSMD8 (HGNC:9566): (proteasome 26S subunit, non-ATPase 8) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD8	NM_002812.5	c.804-422C>A		intron_variant	Intron 5 of 6	ENST00000215071.9	NP_002803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD8	ENST00000215071.9	c.804-422C>A		intron_variant	Intron 5 of 6	1	NM_002812.5	ENSP00000215071.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18118 AN: 152124 Hom.: 1362 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18157 AN: 152242 Hom.: 1360 Cov.: 32 AF XY: 0.119 AC XY: 8851 AN XY: 74424

African (AFR) AF: 0.193 AC: 8019 AN: 41522

American (AMR) AF: 0.131 AC: 2000 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1273 AN: 5174

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4830

European-Finnish (FIN) AF: 0.0645 AC: 685 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5223 AN: 68020

Other (OTH) AF: 0.110 AC: 233 AN: 2116

Alfa AF: 0.0939 Hom.: 989

Bravo AF: 0.128

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.054
DANN	Benign	0.51
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2074981; hg19: chr19-38872335;