rs2305481

Positions:

• chr17-39982371-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002809.4(PSMD3):​c.220+1181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,024 control chromosomes in the GnomAD database, including 8,851 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 0.33 (8851 hom., cov: 33)
• Consequence: PSMD3 NM_002809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

Genes affected

PSMD3 (HGNC:9560): (proteasome 26S subunit, non-ATPase 3) 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. This gene encodes a member of the proteasome subunit S3 family that functions as one of the non-ATPase subunits of the 19S regulator lid. Single nucleotide polymorphisms in this gene are associated with neutrophil count. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD3	NM_002809.4	c.220+1181G>A		intron_variant		ENST00000264639.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD3	ENST00000264639.9	c.220+1181G>A		intron_variant		1	NM_002809.4	P1
PSMD3	ENST00000415039.7	c.120+1281G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49736 AN: 151906 Hom.: 8852 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.327 AC: 49748 AN: 152024 Hom.: 8851 Cov.: 33 AF XY: 0.330 AC XY: 24509 AN XY: 74288

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.374

Alfa AF: 0.332 Hom.: 1103

Bravo AF: 0.328

Asia WGS AF: 0.423 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.23

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: rs2305481; hg19: chr17-38138624;