chr11-237087-A-G

Position:

• chr11-237087-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532097.6(PSMD13):​c.38A>G​(p.Asn13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,486 control chromosomes in the GnomAD database, including 474,032 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.79 (48255 hom., cov: 34)
  • Exomes 𝑓: 0.76 (425777 hom.)
• Consequence: PSMD13 ENST00000532097.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.1342896E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.38A>G	p.Asn13Ser	missense_variant	1/13	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.38A>G	p.Asn13Ser	missense_variant	1/11		NP_787128.2
PSMD13	XM_011520235.4	c.38A>G	p.Asn13Ser	missense_variant	1/11		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.38A>G	p.Asn13Ser	missense_variant	1/13	1	NM_002817.4	ENSP00000436186	P1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120746 AN: 152166 Hom.: 48204 Cov.: 34

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.761

GnomAD3 exomes AF: 0.778 AC: 193409 AN: 248438 Hom.: 75635 AF XY: 0.773 AC XY: 104077 AN XY: 134676

Gnomad AFR exome AF: 0.886

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.826

Gnomad SAS exome AF: 0.792

Gnomad FIN exome AF: 0.763

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.753

GnomAD4 exome AF: 0.763 AC: 1114413 AN: 1461202 Hom.: 425777 Cov.: 55 AF XY: 0.762 AC XY: 553709 AN XY: 726934

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.835

Gnomad4 SAS exome AF: 0.791

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.794 AC: 120849 AN: 152284 Hom.: 48255 Cov.: 34 AF XY: 0.796 AC XY: 59286 AN XY: 74446

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.756

Alfa AF: 0.750 Hom.: 79307

Bravo AF: 0.802

ESP6500AA AF: 0.883 AC: 3892

ESP6500EA AF: 0.744 AC: 6398

ExAC AF: 0.777 AC: 94334

Asia WGS AF: 0.807 AC: 2807 AN: 3478

EpiCase AF: 0.738

EpiControl AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.0014	T;.;T;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.19	T;T;T;T;T
MetaRNN	Benign	7.1e-7	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N;N;.;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.21	N;N;N;.;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.081
MPC		0.27
ClinPred		0.0041	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.054

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

Publications

LitVar

Other links and lift over

dbSNP: rs1045288; hg19: chr11-237087; COSMIC: COSV61500926; COSMIC: COSV61500926;