NM_032302.4:c.256G>T

Variant names:

• chr7-1567811-C-A
• NM_032302.4:c.256G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032302.4(PSMG3):​c.256G>T​(p.Val86Leu) variant causes a missense change. 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: 32)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• Publications: 0 publications found

Genes affected

PSMG3 (HGNC:22420): (proteasome assembly chaperone 3) Enables molecular adaptor activity. Involved in chaperone-mediated protein complex assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032302.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMG3	NM_032302.4	MANE Select	c.256G>T	p.Val86Leu	missense	Exon 2 of 2	NP_115678.1	Q9BT73
	PSMG3	NM_001134340.2		c.256G>T	p.Val86Leu	missense	Exon 3 of 3	NP_001127812.1	Q9BT73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMG3	ENST00000288607.3	TSL:1 MANE Select	c.256G>T	p.Val86Leu	missense	Exon 2 of 2	ENSP00000288607.2	Q9BT73
	PSMG3	ENST00000252329.3	TSL:3	c.256G>T	p.Val86Leu	missense	Exon 3 of 3	ENSP00000252329.3	Q9BT73
	PSMG3	ENST00000404674.7	TSL:2	c.256G>T	p.Val86Leu	missense	Exon 3 of 3	ENSP00000384799.3	Q9BT73

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.63		Loss of sheet (P = 0.0142)
MVP		0.45
MPC		0.96
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.61
gMVP		0.68
Mutation Taster		=21/79	disease causing

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

Other links and lift over

hg19: chr7-1607447;