Genetic Variant PSMG3:p.Thr4Met (chr7-1569329-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032302.4(PSMG3):c.11C>T(p.Thr4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,605,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PSMG3
NM_032302.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127

Variant links:

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]

PSMG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022946596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMG3	NM_032302.4 link	c.11C>T	p.Thr4Met	missense_variant	Exon 1 of 2	ENST00000288607.3	NP_115678.1	Q9BT73A0A024R806
PSMG3	NM_001134340.2 link	c.11C>T	p.Thr4Met	missense_variant	Exon 2 of 3		NP_001127812.1	Q9BT73A0A024R806

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSMG3	ENST00000288607.3 link	c.11C>T	p.Thr4Met	missense_variant	Exon 1 of 2	1	NM_032302.4	ENSP00000288607.2	Q9BT73
PSMG3	ENST00000252329.3 link	c.11C>T	p.Thr4Met	missense_variant	Exon 2 of 3	3		ENSP00000252329.3	Q9BT73
PSMG3	ENST00000404674.7 link	c.11C>T	p.Thr4Met	missense_variant	Exon 2 of 3	2		ENSP00000384799.3	Q9BT73

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000829

AC:

AN:

241188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453628

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722534

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11C>T (p.T4M) alteration is located in exon 1 (coding exon 1) of the PSMG3 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the threonine (T) at amino acid position 4 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.5

DANN

Benign

0.81

DEOGEN2

Benign

0.024

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.30

.;.;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.020

B;B;B

Vest4

0.074

MVP

0.040

MPC

0.40

ClinPred

0.059

GERP RS

-5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.041

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over