rs9916279

Variant names:

• chr17-39989901-T-C
• rs9916279
• NM_002809.4:c.849T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002809.4(PSMD3):​c.849T>C​(p.Asn283Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,698 control chromosomes in the GnomAD database, including 23,892 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 0.20 (3880 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20012 hom.)
• Consequence: PSMD3 NM_002809.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 24 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):

LOC124904000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.849T>C	p.Asn283Asn	synonymous_variant	Exon 5 of 12	ENST00000264639.9	NP_002800.2
LOC124904000	XR_007065751.1	n.3356-1006A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.849T>C	p.Asn283Asn	synonymous_variant	Exon 5 of 12	1	NM_002809.4	ENSP00000264639.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30628 AN: 152008 Hom.: 3880 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.140 AC: 35112 AN: 251178 AF XY: 0.135

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.00725

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.156 AC: 228571 AN: 1461572 Hom.: 20012 Cov.: 33 AF XY: 0.153 AC XY: 111575 AN XY: 727036

African (AFR) AF: 0.361 AC: 12092 AN: 33474

American (AMR) AF: 0.0911 AC: 4073 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3039 AN: 26134

East Asian (EAS) AF: 0.00328 AC: 130 AN: 39664

South Asian (SAS) AF: 0.0736 AC: 6347 AN: 86252

European-Finnish (FIN) AF: 0.155 AC: 8268 AN: 53400

Middle Eastern (MID) AF: 0.115 AC: 662 AN: 5736

European-Non Finnish (NFE) AF: 0.166 AC: 184988 AN: 1111808

Other (OTH) AF: 0.149 AC: 8972 AN: 60386

GnomAD4 genome AF: 0.201 AC: 30648 AN: 152126 Hom.: 3880 Cov.: 32 AF XY: 0.197 AC XY: 14632 AN XY: 74374

African (AFR) AF: 0.347 AC: 14407 AN: 41472

American (AMR) AF: 0.144 AC: 2193 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4824

European-Finnish (FIN) AF: 0.149 AC: 1578 AN: 10584

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11170 AN: 68002

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.170 Hom.: 3570

Bravo AF: 0.208

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9916279; hg19: chr17-38146154; COSMIC: COSV52857676; COSMIC: COSV52857676;