17-39983981-C-G

Variant names:

• chr17-39983981-C-G
• rs11078929
• NM_002809.4:c.221-313C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002809.4(PSMD3):​c.221-313C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,000 control chromosomes in the GnomAD database, including 56,555 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 0.86 (56555 hom., cov: 31)
• Consequence: PSMD3 NM_002809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.221-313C>G		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.221-313C>G		intron_variant	Intron 1 of 11	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000415039.7	n.121-478C>G		intron_variant	Intron 1 of 12	2		ENSP00000407410.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130865 AN: 151882 Hom.: 56499 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.897

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.862 AC: 130980 AN: 152000 Hom.: 56555 Cov.: 31 AF XY: 0.858 AC XY: 63733 AN XY: 74308

African (AFR) AF: 0.915 AC: 37953 AN: 41458

American (AMR) AF: 0.843 AC: 12892 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2894 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4663 AN: 5144

South Asian (SAS) AF: 0.765 AC: 3679 AN: 4812

European-Finnish (FIN) AF: 0.819 AC: 8643 AN: 10556

Middle Eastern (MID) AF: 0.900 AC: 261 AN: 290

European-Non Finnish (NFE) AF: 0.845 AC: 57426 AN: 67970

Other (OTH) AF: 0.863 AC: 1820 AN: 2108

Alfa AF: 0.839 Hom.: 2618

Bravo AF: 0.872

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.27
PhyloP100		-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: rs11078929; hg19: chr17-38140234;