Variant 9-120817982-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005047.4(PSMD5):c.1439G>A(p.Arg480Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,614,192 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 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

PSMD5
NM_005047.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

PSMD5 (HGNC:9563): (proteasome 26S subunit, non-ATPase 5) 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. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]

PSMD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02957207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD5	NM_005047.4 linkuse as main transcript	c.1439G>A	p.Arg480Lys	missense_variant	10/10	ENST00000210313.8	NP_005038.1	Q16401-1
PSMD5	NM_001270427.2 linkuse as main transcript	c.1310G>A	p.Arg437Lys	missense_variant	9/9		NP_001257356.1	Q16401-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSMD5	ENST00000210313.8 linkuse as main transcript	c.1439G>A	p.Arg480Lys	missense_variant	10/10	1	NM_005047.4	ENSP00000210313.2	Q16401-1
PSMD5	ENST00000373904.5 linkuse as main transcript	c.1310G>A	p.Arg437Lys	missense_variant	9/9	2		ENSP00000363011.5	Q16401-2
PSMD5	ENST00000373920.6 linkuse as main transcript	c.277-2194G>A		intron_variant		5		ENSP00000363030.2	Q4VXH0

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000956

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251424

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.000145

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:

0.000326

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.000112

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:

0.000116

GnomAD4 genome

AF:

0.000499

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.000196

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:

0.000947

Alfa

AF:

0.0000777

Hom.:

Bravo

AF:

0.000589

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

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 14, 2021

The c.1439G>A (p.R480K) alteration is located in exon 10 (coding exon 10) of the PSMD5 gene. This alteration results from a G to A substitution at nucleotide position 1439, causing the arginine (R) at amino acid position 480 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

0.095

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.068

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.061

Sift

Benign

0.24

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.24

B;.

Vest4

0.11

MVP

0.41

MPC

0.46

ClinPred

0.025

GERP RS

4.1

Varity_R

0.087

gMVP

0.55

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.

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