Variant 21-39180355-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003720.4(PSMG1):c.323C>T(p.Thr108Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000989 in 1,612,756 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

PSMG1
NM_003720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

PSMG1 (HGNC:3043): (proteasome assembly chaperone 1) Enables molecular adaptor activity. Involved in chaperone-mediated protein complex assembly. Located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and nucleoplasm. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

PSMG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30187076).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG1	NM_003720.4 linkuse as main transcript	c.323C>T	p.Thr108Ile	missense_variant	3/7	ENST00000331573.8	NP_003711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMG1	ENST00000331573.8 linkuse as main transcript	c.323C>T	p.Thr108Ile	missense_variant	3/7	1	NM_003720.4	ENSP00000329915	P1	O95456-1
PSMG1	ENST00000380900.2 linkuse as main transcript	c.323C>T	p.Thr108Ile	missense_variant	3/6	1		ENSP00000370286		O95456-2
PSMG1	ENST00000431628.1 linkuse as main transcript	c.*24C>T		3_prime_UTR_variant, NMD_transcript_variant	2/6	1		ENSP00000398569
PSMG1	ENST00000411828.5 linkuse as main transcript	c.*373C>T		3_prime_UTR_variant, NMD_transcript_variant	3/7	3		ENSP00000410810

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000542

AC:

136

AN:

250748

Hom.:

AF XY:

0.000480

AC XY:

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.000508

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00103

AC:

1500

AN:

1460446

Hom.:

Cov.:

AF XY:

0.000979

AC XY:

711

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000624

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000831

Hom.:

Bravo

AF:

0.000502

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000585

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.323C>T (p.T108I) alteration is located in exon 3 (coding exon 3) of the PSMG1 gene. This alteration results from a C to T substitution at nucleotide position 323, causing the threonine (T) at amino acid position 108 to be replaced by an isoleucine (I). 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

0.26

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.93

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.21

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.046

D;T

Polyphen

1.0

D;D

Vest4

0.64

MVP

0.74

MPC

0.82

ClinPred

0.14

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.39

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

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