chr16-74301636-G-A

Variant summary

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

The NM_002811.5(PSMD7):​c.341G>A​(p.Arg114Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,611,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PSMD7
NM_002811.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01
Variant links:
Genes affected
PSMD7 (HGNC:9565): (proteasome 26S subunit, non-ATPase 7) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

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=0.3517329).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMD7NM_002811.5 linkuse as main transcriptc.341G>A p.Arg114Lys missense_variant 4/7 ENST00000219313.9 NP_002802.2 P51665

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMD7ENST00000219313.9 linkuse as main transcriptc.341G>A p.Arg114Lys missense_variant 4/71 NM_002811.5 ENSP00000219313.4 P51665

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459324
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726160
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
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:
0.00000756

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 GeneticsSep 26, 2023The c.341G>A (p.R114K) alteration is located in exon 4 (coding exon 4) of the PSMD7 gene. This alteration results from a G to A substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a lysine (K). 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
0.14
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.24
T;T;T
Eigen
Benign
-0.013
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.61
N;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.31
T;T;T
Sift4G
Benign
0.64
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.56
MutPred
0.55
Gain of methylation at R114 (P = 0.0062);Gain of methylation at R114 (P = 0.0062);Gain of methylation at R114 (P = 0.0062);
MVP
0.40
MPC
0.46
ClinPred
0.76
D
GERP RS
5.7
Varity_R
0.69
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs764226241; hg19: chr16-74335534; API