NM_002809.4:c.411+190A>C

Variant names:

• chr17-39984674-A-C
• rs2305482
• NM_002809.4:c.411+190A>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.411+190A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,964 control chromosomes in the GnomAD database, including 24,472 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 0.56 (24472 hom., cov: 31)
• Consequence: PSMD3 NM_002809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD3	NM_002809.4	MANE Select	c.411+190A>C		intron	N/A	NP_002800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD3	ENST00000264639.9	TSL:1 MANE Select	c.411+190A>C		intron	N/A	ENSP00000264639.4	O43242-1
	PSMD3	ENST00000916285.1		c.411+190A>C		intron	N/A	ENSP00000586344.1
	PSMD3	ENST00000916290.1		c.411+190A>C		intron	N/A	ENSP00000586349.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85703 AN: 151846 Hom.: 24460 Cov.: 31

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.564 AC: 85757 AN: 151964 Hom.: 24472 Cov.: 31 AF XY: 0.560 AC XY: 41559 AN XY: 74276

African (AFR) AF: 0.641 AC: 26556 AN: 41428

American (AMR) AF: 0.569 AC: 8686 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2200 AN: 5162

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4985 AN: 10558

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36911 AN: 67948

Other (OTH) AF: 0.591 AC: 1249 AN: 2112

Alfa AF: 0.565 Hom.: 4281

Bravo AF: 0.578

Asia WGS AF: 0.506 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
DANN	Benign	0.50
PhyloP100		-2.0
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: rs2305482; hg19: chr17-38140927;