Variant 21-39177451-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003720.4(PSMG1):c.776T>G(p.Leu259Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,597,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PSMG1
NM_003720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

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:

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ACMG classification

Classification made for transcript

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=0.07226506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG1	NM_003720.4 linkuse as main transcript	c.776T>G	p.Leu259Trp	missense_variant	6/7	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.776T>G	p.Leu259Trp	missense_variant	6/7	1	NM_003720.4	ENSP00000329915	P1	O95456-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

236414

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

127852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000993

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445168

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718528

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000245

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000151

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000196

ExAC

AF:

0.0000165

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

Aug 30, 2021

The c.776T>G (p.L259W) alteration is located in exon 6 (coding exon 6) of the PSMG1 gene. This alteration results from a T to G substitution at nucleotide position 776, causing the leucine (L) at amino acid position 259 to be replaced by a tryptophan (W). 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

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.41

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

D;N

REVEL

Benign

0.16

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.033

D;D

Polyphen

0.042

B;B

Vest4

0.35

MutPred

0.64

Gain of MoRF binding (P = 0.0244);.;

MVP

0.49

MPC

0.39

ClinPred

0.74

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.82

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