rs1177573

Variant names:

• chr12-121899792-C-T
• rs1177573
• NM_002813.7:c.400C>T

Variant summary

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

The NM_002813.7(PSMD9):​c.400C>T​(p.Arg134Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,614,064 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (324 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (297 hom.)
• Consequence: PSMD9 NM_002813.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 10 publications found

Genes affected

PSMD9 (HGNC:9567): (proteasome 26S subunit, non-ATPase 9) 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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ENSG00000256950 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016908348).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002813.7. 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
	PSMD9	NM_002813.7	MANE Select	c.400C>T	p.Arg134Trp	missense	Exon 3 of 6	NP_002804.2
	PSMD9	NM_001261400.3		c.139-3214C>T		intron	N/A	NP_001248329.1	O00233-3
	PSMD9	NR_048555.3		n.309-3214C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD9	ENST00000541212.6	TSL:1 MANE Select	c.400C>T	p.Arg134Trp	missense	Exon 3 of 6	ENSP00000440485.1	O00233-1
	PSMD9	ENST00000537407.5	TSL:1	n.400C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000445058.1	O00233-2
	ENSG00000256950	ENST00000546333.1	TSL:5	n.242-3214C>T		intron	N/A	ENSP00000477146.1	F5H7X1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5563 AN: 152218 Hom.: 323 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000749

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0100 AC: 2517 AN: 250780 AF XY: 0.00757

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00766

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.000716

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00405 AC: 5923 AN: 1461728 Hom.: 297 Cov.: 30 AF XY: 0.00352 AC XY: 2557 AN XY: 727174

African (AFR) AF: 0.131 AC: 4388 AN: 33472

American (AMR) AF: 0.00917 AC: 410 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86250

European-Finnish (FIN) AF: 0.000543 AC: 29 AN: 53404

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5764

European-Non Finnish (NFE) AF: 0.000403 AC: 448 AN: 1111910

Other (OTH) AF: 0.00949 AC: 573 AN: 60380

GnomAD4 genome AF: 0.0366 AC: 5576 AN: 152336 Hom.: 324 Cov.: 33 AF XY: 0.0360 AC XY: 2681 AN XY: 74488

African (AFR) AF: 0.126 AC: 5247 AN: 41560

American (AMR) AF: 0.0146 AC: 224 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68042

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0263 Hom.: 222

Bravo AF: 0.0418

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.123 AC: 544

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0122 AC: 1480

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.16
MPC		0.53
ClinPred		0.044	T
GERP RS		1.7
Varity_R		0.064
gMVP		0.32
Mutation Taster		=100/0	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: rs1177573; hg19: chr12-122337698; COSMIC: COSV106324964; COSMIC: COSV106324964;