rs1794108

Variant names:

• chr11-248818-G-A
• rs1794108
• NM_002817.4:c.611G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-248818-G-A
• chr11-248818-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002817.4(PSMD13):​c.611G>A​(p.Gly204Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMD13 NM_002817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.87
• Publications: 8 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.611G>A	p.Gly204Glu	missense_variant	Exon 8 of 13	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.617G>A	p.Gly206Glu	missense_variant	Exon 6 of 11		NP_787128.2
PSMD13	XM_011520235.4	c.611G>A	p.Gly204Glu	missense_variant	Exon 8 of 11		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.611G>A	p.Gly204Glu	missense_variant	Exon 8 of 13	1	NM_002817.4	ENSP00000436186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;T;.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.;.;.
PhyloP100		9.9
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.0	N;N;N;.;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D;D;D;.;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		0.99	D;D;.;.;.
Vest4		0.86
MutPred		0.86		Loss of catalytic residue at A203 (P = 0.0485);.;.;Loss of catalytic residue at A203 (P = 0.0485);Loss of catalytic residue at A203 (P = 0.0485);
MVP		0.76
MPC		1.1
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.79
gMVP		0.96
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1794108; hg19: chr11-248818;