NM_032302.4:c.55G>T

Variant names:

• chr7-1569285-C-A
• rs756874928
• NM_032302.4:c.55G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032302.4(PSMG3):​c.55G>T​(p.Val19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,732 control chromosomes in the GnomAD database, including 1 homozygotes. 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. V19I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (1 hom.)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.55G>T	p.Val19Phe	missense	Exon 1 of 2	NP_115678.1	Q9BT73
	PSMG3	NM_001134340.2		c.55G>T	p.Val19Phe	missense	Exon 2 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.55G>T	p.Val19Phe	missense	Exon 1 of 2	ENSP00000288607.2	Q9BT73
	PSMG3	ENST00000252329.3	TSL:3	c.55G>T	p.Val19Phe	missense	Exon 2 of 3	ENSP00000252329.3	Q9BT73
	PSMG3	ENST00000404674.7	TSL:2	c.55G>T	p.Val19Phe	missense	Exon 2 of 3	ENSP00000384799.3	Q9BT73

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 249982 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460732 Hom.: 1 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726640

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39686

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5360

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.39		Loss of sheet (P = 0.1398)
MVP		0.24
MPC		0.78
ClinPred		0.34	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.70
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs756874928; hg19: chr7-1608921;