NM_002817.4:c.175-773T>G

Variant names:

• chr11-243268-T-G
• rs505404
• NM_002817.4:c.175-773T>G

Variant summary

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

The NM_002817.4(PSMD13):​c.175-773T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 438,562 control chromosomes in the GnomAD database, including 14,494 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 0.27 (6824 hom., cov: 32)
  • Exomes 𝑓: 0.21 (7670 hom.)
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 33 publications found

Genes affected

PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ENSG00000277290 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.175-773T>G		intron_variant	Intron 2 of 12	ENST00000532097.6	NP_002808.3
LOC100420679		n.243268T>G		intragenic_variant
PSMD13	NM_175932.3	c.96-773T>G		intron_variant	Intron 1 of 10		NP_787128.2
PSMD13	XM_011520235.4	c.175-773T>G		intron_variant	Intron 2 of 10		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.175-773T>G		intron_variant	Intron 2 of 12	1	NM_002817.4	ENSP00000436186.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41643 AN: 151980 Hom.: 6811 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00499

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.210 AC: 60237 AN: 286464 Hom.: 7670 Cov.: 0 AF XY: 0.199 AC XY: 32211 AN XY: 162192

African (AFR) AF: 0.453 AC: 3727 AN: 8236

American (AMR) AF: 0.253 AC: 5250 AN: 20716

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 877 AN: 7074

East Asian (EAS) AF: 0.00200 AC: 31 AN: 15492

South Asian (SAS) AF: 0.0862 AC: 3865 AN: 44856

European-Finnish (FIN) AF: 0.290 AC: 7897 AN: 27186

Middle Eastern (MID) AF: 0.115 AC: 110 AN: 954

European-Non Finnish (NFE) AF: 0.239 AC: 35594 AN: 148888

Other (OTH) AF: 0.221 AC: 2886 AN: 13062

GnomAD4 genome AF: 0.274 AC: 41706 AN: 152098 Hom.: 6824 Cov.: 32 AF XY: 0.272 AC XY: 20223 AN XY: 74354

African (AFR) AF: 0.452 AC: 18762 AN: 41468

American (AMR) AF: 0.214 AC: 3268 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.00481 AC: 25 AN: 5194

South Asian (SAS) AF: 0.0808 AC: 389 AN: 4816

European-Finnish (FIN) AF: 0.286 AC: 3025 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15127 AN: 67982

Other (OTH) AF: 0.238 AC: 502 AN: 2106

Alfa AF: 0.238 Hom.: 10087

Bravo AF: 0.280

Asia WGS AF: 0.0760 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.7
DANN	Benign	0.43
PhyloP100		-0.0050
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: rs505404; hg19: chr11-243268;