rs7021

Variant names:

• chr17-39997622-T-A
• rs7021
• NM_002809.4:c.*41T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39997622-T-A
• chr17-39997622-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

ENSG00000265799 (HGNC:58140):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.*41T>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000264639.9	NP_002800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.*41T>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000540504.2	c.295-172T>A		intron_variant	Intron 3 of 3	3		ENSP00000444980.2
ENSG00000265799	ENST00000801108.1	n.538-8727A>T		intron_variant	Intron 2 of 3
PSMD3	ENST00000415039.7	n.*1213T>A		downstream_gene_variant		2		ENSP00000407410.3

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

GnomAD2 exomes AF: 0.361 AC: 84134 AN: 233054 AF XY: 0.357

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 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

African (AFR) AF: 0.275 AC: 8527 AN: 30992

American (AMR) AF: 0.330 AC: 14420 AN: 43742

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8399 AN: 25082

East Asian (EAS) AF: 0.490 AC: 18926 AN: 38624

South Asian (SAS) AF: 0.254 AC: 21131 AN: 83346

European-Finnish (FIN) AF: 0.388 AC: 19792 AN: 51036

Middle Eastern (MID) AF: 0.248 AC: 1248 AN: 5026

European-Non Finnish (NFE) AF: 0.364 AC: 358064 AN: 983522

Other (OTH) AF: 0.361 AC: 19976 AN: 55320

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

African (AFR) AF: 0.297 AC: 12313 AN: 41452

American (AMR) AF: 0.337 AC: 5150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2374 AN: 5156

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4197 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26538 AN: 67926

Other (OTH) AF: 0.335 AC: 706 AN: 2106

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
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7021; hg19: chr17-38153875; COSMIC: COSV99227669; COSMIC: COSV99227669;