NM_002809.4:c.220+1181G>A

Variant names:

• chr17-39982371-G-A
• rs2305481
• NM_002809.4:c.220+1181G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.220+1181G>A		intron_variant	Intron 1 of 11	ENST00000264639.9	NP_002800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.220+1181G>A		intron_variant	Intron 1 of 11	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000415039.7	n.120+1281G>A		intron_variant	Intron 1 of 12	2		ENSP00000407410.3

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

African (AFR) AF: 0.183 AC: 7590 AN: 41466

American (AMR) AF: 0.404 AC: 6177 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1456 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2143 AN: 5174

South Asian (SAS) AF: 0.470 AC: 2269 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3545 AN: 10532

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25328 AN: 67956

Other (OTH) AF: 0.374 AC: 790 AN: 2112

Alfa AF: 0.356 Hom.: 12103

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
PhyloP100		0.15
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: rs2305481; hg19: chr17-38138624;