rs7021

Positions:

• chr17-39997622-T-A

Variant summary

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

The NM_002809.4(PSMD3):​c.*41T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,468,704 control chromosomes in the GnomAD database, including 102,174 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 0.36 (9807 hom., cov: 32)
  • Exomes 𝑓: 0.36 (92367 hom.)
• Consequence: PSMD3 NM_002809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.*41T>A		3_prime_UTR_variant	12/12	ENST00000264639.9	NP_002800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.*41T>A		3_prime_UTR_variant	12/12	1	NM_002809.4	ENSP00000264639	P1
PSMD3	ENST00000540504.2	c.297-172T>A		intron_variant		3		ENSP00000444980
PSMD3	ENST00000415039.7			downstream_gene_variant		2		ENSP00000407410

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54097 AN: 151896 Hom.: 9794 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.361 AC: 84134 AN: 233054 Hom.: 15304 AF XY: 0.357 AC XY: 45515 AN XY: 127362

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.326

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.476

Gnomad SAS exome AF: 0.259

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.357 AC: 470483 AN: 1316690 Hom.: 92367 Cov.: 24 AF XY: 0.355 AC XY: 234212 AN XY: 660174

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.356 AC: 54165 AN: 152014 Hom.: 9807 Cov.: 32 AF XY: 0.355 AC XY: 26356 AN XY: 74334

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.335

Alfa AF: 0.369 Hom.: 1936

Bravo AF: 0.350

Asia WGS AF: 0.375 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7021; hg19: chr17-38153875;