17-32473854-T-A

Position:

• chr17-32473854-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002815.4(PSMD11):​c.697T>A​(p.Tyr233Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PSMD11 NM_002815.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

Genes affected

PSMD11 (HGNC:9556): (proteasome 26S subunit, non-ATPase 11) 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 member of the proteasome subunit S9 family that functions as a non-ATPase subunit of the 19S regulator and is phosphorylated by AMP-activated protein kinase. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

PSMD11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD11	NM_002815.4	c.697T>A	p.Tyr233Asn	missense_variant	7/14	ENST00000261712.8	NP_002806.2
PSMD11	NM_001270482.2	c.697T>A	p.Tyr233Asn	missense_variant	7/13		NP_001257411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD11	ENST00000261712.8	c.697T>A	p.Tyr233Asn	missense_variant	7/14	1	NM_002815.4	ENSP00000261712.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	29
DANN	Benign	0.90
DEOGEN2	Uncertain	0.44	T;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	.;.;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.7	H;H;H
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-7.8	D;.;.
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0	D;.;D
Polyphen		0.97	D;D;D
Vest4		0.77
MutPred		0.62		Loss of stability (P = 0.0939);Loss of stability (P = 0.0939);Loss of stability (P = 0.0939);
MVP		0.53
MPC		2.3
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.96
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-30800872;