chr6-3259074-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128591.2(PSMG4):ā€‹c.52A>Gā€‹(p.Ser18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000473 in 1,268,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000036 ( 0 hom. )

Consequence

PSMG4
NM_001128591.2 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
Variant links:
Genes affected
PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40798336).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMG4NM_001128591.2 linkuse as main transcriptc.52A>G p.Ser18Gly missense_variant 1/3 ENST00000438998.7 NP_001122063.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMG4ENST00000438998.7 linkuse as main transcriptc.52A>G p.Ser18Gly missense_variant 1/32 NM_001128591.2 ENSP00000413353 P1Q5JS54-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152018
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
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
GnomAD4 exome
AF:
0.00000358
AC:
4
AN:
1115930
Hom.:
0
Cov.:
31
AF XY:
0.00000188
AC XY:
1
AN XY:
531700
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000375
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000320
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152130
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000389
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsDec 17, 2021The c.52A>G (p.S18G) alteration is located in exon 1 (coding exon 1) of the PSMG4 gene. This alteration results from a A to G substitution at nucleotide position 52, causing the serine (S) at amino acid position 18 to be replaced by a glycine (G). 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;.;.;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.80
T;T;T;T;T
M_CAP
Pathogenic
0.97
D
MetaRNN
Benign
0.41
T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Uncertain
2.8
M;.;M;M;.
MutationTaster
Benign
0.98
D;D;D;D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-2.3
N;D;N;D;D
REVEL
Benign
0.16
Sift
Benign
0.040
D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D
Polyphen
0.96
D;.;.;.;.
Vest4
0.22
MutPred
0.27
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
0.014
ClinPred
0.93
D
GERP RS
4.8
Varity_R
0.47
gMVP
0.18

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.

Other links and lift over

dbSNP: rs1473812732; hg19: chr6-3259308; COSMIC: COSV61476473; API