1-151400125-G-T

Position:

• chr1-151400125-G-T

Variant summary

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

The NM_002796.3(PSMB4):​c.285G>T​(p.Met95Ile) 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M95T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMB4 NM_002796.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

Genes affected

PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) 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. [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=0.08255157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB4	NM_002796.3	c.285G>T	p.Met95Ile	missense_variant	2/7	ENST00000290541.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB4	ENST00000290541.7	c.285G>T	p.Met95Ile	missense_variant	2/7	1	NM_002796.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.5	N
MutationTaster	Benign	0.81	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.072
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.49		Loss of MoRF binding (P = 0.1025);
MVP		0.17
MPC		0.49
ClinPred		0.68	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.44

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: rs1804241; hg19: chr1-151372601;