9-120824459-T-G

Variant names:

• chr9-120824459-T-G
• rs10760117
• NM_005047.4:c.1006+35A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005047.4(PSMD5):​c.1006+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,601,154 control chromosomes in the GnomAD database, including 274,835 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 0.49 (20646 hom., cov: 32)
  • Exomes 𝑓: 0.59 (254189 hom.)
• Consequence: PSMD5 NM_005047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 53 publications found

Genes affected

PSMD5 (HGNC:9563): (proteasome 26S subunit, non-ATPase 5) 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 non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.028).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD5	NM_005047.4	MANE Select	c.1006+35A>C		intron	N/A	NP_005038.1
	PSMD5	NM_001270427.2		c.877+35A>C		intron	N/A	NP_001257356.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD5	ENST00000210313.8	TSL:1 MANE Select	c.1006+35A>C		intron	N/A	ENSP00000210313.2
	PSMD5	ENST00000373903.1	TSL:3	n.357A>C		non_coding_transcript_exon	Exon 2 of 2
	PSMD5	ENST00000373904.5	TSL:2	c.877+35A>C		intron	N/A	ENSP00000363011.5

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74645 AN: 151908 Hom.: 20633 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.593 AC: 148303 AN: 250076 AF XY: 0.604

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.718

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.483

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.594

GnomAD4 exome AF: 0.586 AC: 849589 AN: 1449128 Hom.: 254189 Cov.: 31 AF XY: 0.592 AC XY: 427505 AN XY: 721754

African (AFR) AF: 0.204 AC: 6750 AN: 33128

American (AMR) AF: 0.710 AC: 31727 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16857 AN: 26064

East Asian (EAS) AF: 0.427 AC: 16902 AN: 39628

South Asian (SAS) AF: 0.737 AC: 63293 AN: 85890

European-Finnish (FIN) AF: 0.589 AC: 31453 AN: 53398

Middle Eastern (MID) AF: 0.645 AC: 3709 AN: 5746

European-Non Finnish (NFE) AF: 0.586 AC: 644564 AN: 1100574

Other (OTH) AF: 0.572 AC: 34334 AN: 60016

GnomAD4 genome AF: 0.491 AC: 74677 AN: 152026 Hom.: 20646 Cov.: 32 AF XY: 0.499 AC XY: 37107 AN XY: 74304

African (AFR) AF: 0.222 AC: 9188 AN: 41466

American (AMR) AF: 0.629 AC: 9609 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2267 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2467 AN: 5176

South Asian (SAS) AF: 0.736 AC: 3542 AN: 4812

European-Finnish (FIN) AF: 0.588 AC: 6211 AN: 10554

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39719 AN: 67966

Other (OTH) AF: 0.538 AC: 1136 AN: 2112

Alfa AF: 0.559 Hom.: 88452

Bravo AF: 0.480

Asia WGS AF: 0.582 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.66
PhyloP100		0.11
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10760117; hg19: chr9-123586737; COSMIC: COSV52960569; COSMIC: COSV52960569;