6-3264247-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001128591.2(PSMG4):​c.250+488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,551,476 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PSMG4
NM_001128591.2 intron

Scores

16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.98
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0054430068).
BP6
Variant 6-3264247-G-A is Benign according to our data. Variant chr6-3264247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2356268.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMG4NM_001128591.2 linkuse as main transcriptc.250+488G>A intron_variant ENST00000438998.7 NP_001122063.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMG4ENST00000438998.7 linkuse as main transcriptc.250+488G>A intron_variant 2 NM_001128591.2 ENSP00000413353 P1Q5JS54-1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152224
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000344
AC:
53
AN:
154102
Hom.:
0
AF XY:
0.000355
AC XY:
29
AN XY:
81740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00126
Gnomad ASJ exome
AF:
0.00165
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000878
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000101
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000126
AC:
176
AN:
1399134
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
93
AN XY:
690094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.00226
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.000101
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000408
Gnomad4 OTH exome
AF:
0.000362
GnomAD4 genome
AF:
0.000203
AC:
31
AN:
152342
Hom.:
0
Cov.:
34
AF XY:
0.000228
AC XY:
17
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000230
Hom.:
0
Bravo
AF:
0.000246
ExAC
AF:
0.000280
AC:
7

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.014
DANN
Benign
0.74
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.00088
T
MetaRNN
Benign
0.0054
T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.070
N
REVEL
Benign
0.0070
Sift
Benign
0.44
T
Sift4G
Benign
0.32
T
Vest4
0.090
MVP
0.014
ClinPred
0.0093
T
GERP RS
-4.2
gMVP
0.058

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: rs566254513; hg19: chr6-3264481; API