11-237087-A-C

Position:

• chr11-237087-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000532097.6(PSMD13):​c.38A>C​(p.Asn13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N13S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091121644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.38A>C	p.Asn13Thr	missense_variant	1/13	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.38A>C	p.Asn13Thr	missense_variant	1/11		NP_787128.2
PSMD13	XM_011520235.4	c.38A>C	p.Asn13Thr	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>C	p.Asn13Thr	missense_variant	1/13	1	NM_002817.4	ENSP00000436186	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0019	T;.;T;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.61	T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.091	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N;N;.;.;.
MutationTaster	Benign	0.99	P;P;P
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.41	N;N;N;.;N
REVEL	Benign	0.071
Sift	Benign	0.48	T;T;D;.;T
Sift4G	Benign	0.58	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.21
MutPred		0.21		Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP		0.25
MPC		0.37
ClinPred		0.66	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.11

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;