rs9916279

Positions:

• chr17-39989901-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002809.4(PSMD3):​c.849T>C​(p.Asn283=) 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

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]

LOC124904000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PSMD3	NM_002809.4	c.849T>C	p.Asn283=	synonymous_variant	5/12	ENST00000264639.9
LOC124904000	XR_007065751.1	n.3356-1006A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD3	ENST00000264639.9	c.849T>C	p.Asn283=	synonymous_variant	5/12	1	NM_002809.4	P1
PSMD3	ENST00000540504.2	c.296+108T>C		intron_variant		3
PSMD3	ENST00000580980.1	n.329T>C		non_coding_transcript_exon_variant	3/3	2
PSMD3	ENST00000415039.7	c.*323T>C		3_prime_UTR_variant, NMD_transcript_variant	5/13	2

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

GnomAD3 exomes AF: 0.140 AC: 35112 AN: 251178 Hom.: 3197 AF XY: 0.135 AC XY: 18288 AN XY: 135756

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 SAS exome AF: 0.0739

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

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.0911

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.00328

Gnomad4 SAS exome AF: 0.0736

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.149

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

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.179

Alfa AF: 0.165 Hom.: 2650

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs9916279; hg19: chr17-38146154; COSMIC: COSV52857676; COSMIC: COSV52857676;