NM_002797.5:c.203G>C

Variant names:

• chr14-23033670-C-G
• NM_002797.5:c.203G>C

Variant summary

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

The NM_002797.5(PSMB5):​c.203G>C​(p.Arg68Pro) 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. R68G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PSMB5 NM_002797.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

Genes affected

PSMB5 (HGNC:9542): (proteasome 20S subunit beta 5) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

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=0.12606105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB5	NM_002797.5	c.203G>C	p.Arg68Pro	missense_variant	Exon 2 of 3	ENST00000361611.11	NP_002788.1
PSMB5	NM_001144932.3	c.203G>C	p.Arg68Pro	missense_variant	Exon 2 of 4		NP_001138404.1
PSMB5	NM_001130725.1	c.-107G>C		5_prime_UTR_variant	Exon 2 of 3		NP_001124197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB5	ENST00000361611.11	c.203G>C	p.Arg68Pro	missense_variant	Exon 2 of 3	1	NM_002797.5	ENSP00000355325.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.095	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.27
Sift	Benign	0.082	T;T
Sift4G	Uncertain	0.027	D;D
Polyphen		0.0	B;B
Vest4		0.25
MutPred		0.48		Gain of catalytic residue at V71 (P = 5e-04);Gain of catalytic residue at V71 (P = 5e-04);
MVP		0.92
MPC		0.81
ClinPred		0.25	T
GERP RS		-6.9
Varity_R		0.78
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-23502879;