Genetic Variant PSMD3:c.981+479T>C (chr17-39990676-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002809.4(PSMD3):c.981+479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,018 control chromosomes in the GnomAD database, including 24,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24194 hom., cov: 31)

Consequence

PSMD3
NM_002809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

19 publications found

Variant links:

Genes affected

PSMD3 (HGNC:9560): (proteasome 26S subunit, non-ATPase 3) 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 member of the proteasome subunit S3 family that functions as one of the non-ATPase subunits of the 19S regulator lid. Single nucleotide polymorphisms in this gene are associated with neutrophil count. [provided by RefSeq, Jul 2012]

PSMD3 links:

ENSG00000265799 (HGNC:58140):

ENSG00000265799 links:

LOC124904000 (HGNC:):

LOC124904000 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD3	NM_002809.4 link	c.981+479T>C		intron_variant	Intron 6 of 11	ENST00000264639.9	NP_002800.2
LOC124904000	XR_007065751.1 link	n.3355+917A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PSMD3	ENST00000264639.9 link	c.981+479T>C	intron_variant	Intron 6 of 11	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000540504.2 link	c.294+883T>C	intron_variant	Intron 3 of 3	3		ENSP00000444980.2
PSMD3	ENST00000415039.7 link	n.*455+479T>C	intron_variant	Intron 6 of 12	2		ENSP00000407410.3
ENSG00000265799	ENST00000801108.1 link	n.538-1781A>G	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85247

AN:

151900

Hom.:

24185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.561

AC:

85299

AN:

152018

Hom.:

24194

Cov.:

AF XY:

0.556

AC XY:

41337

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.639

AC:

26491

AN:

41466

American (AMR)

AF:

0.567

AC:

8662

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1921

AN:

3468

East Asian (EAS)

AF:

0.421

AC:

2172

AN:

5160

South Asian (SAS)

AF:

0.542

AC:

2617

AN:

4828

European-Finnish (FIN)

AF:

0.470

AC:

4965

AN:

10558

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36611

AN:

67944

Other (OTH)

AF:

0.589

AC:

1243

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1934

3868

5803

7737

9671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.561

Hom.:

43178

Bravo

AF:

0.575

Asia WGS

AF:

0.506

AC:

1764

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.8

(source)

DANN

Benign

0.42

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over