Variant X-108087800-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002814.4(PSMD10):c.413A>T(p.Tyr138Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,210,130 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

PSMD10
NM_002814.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

PSMD10 (HGNC:9555): (proteasome 26S subunit, non-ATPase 10) This gene encodes a subunit of the PA700/19S complex, which is the regulatory component of the 26S proteasome. The 26S proteosome complex is required for ubiquitin-dependent protein degradation. This protein is a non-ATPase subunit that may be involved in protein-protein interactions. Aberrant expression of this gene may paly a role in tumorigenesis. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.[provided by RefSeq, Mar 2011]

PSMD10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11613503).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD10	NM_002814.4 link	c.413A>T	p.Tyr138Phe	missense_variant	4/5	ENST00000217958.8	NP_002805.1	O75832-1
PSMD10	NM_170750.3 link	c.413A>T	p.Tyr138Phe	missense_variant	4/5		NP_736606.1	O75832-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD10	ENST00000217958.8 link	c.413A>T	p.Tyr138Phe	missense_variant	4/5	1	NM_002814.4	ENSP00000217958.3		O75832-1

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111929

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34111

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:

0.000278

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:

0.00000364

AC:

AN:

1098201

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363555

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111929

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34111

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000278

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jun 12, 2023

The c.413A>T (p.Y138F) alteration is located in exon 4 (coding exon 4) of the PSMD10 gene. This alteration results from a A to T substitution at nucleotide position 413, causing the tyrosine (Y) at amino acid position 138 to be replaced by a phenylalanine (F). 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

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.021

T;.;.;.;.

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.87

D;D;D;T;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;.;.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.91

N;N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.69

T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.14

MutPred

0.35

Loss of phosphorylation at Y138 (P = 0.0259);.;.;Loss of phosphorylation at Y138 (P = 0.0259);.;

MVP

0.74

MPC

0.37

ClinPred

0.50

GERP RS

4.0

Varity_R

0.27

gMVP

0.26

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