Variant chr17-67340873-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002816.5(PSMD12):c.1341C>A(p.Ala447=) variant causes a synonymous change. The variant allele was found at a frequency of 0.008 in 1,585,742 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0083 ( 71 hom. )

Consequence

PSMD12
NM_002816.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.27

Variant links:

Genes affected

PSMD12 (HGNC:9557): (proteasome 26S subunit, non-ATPase 12) 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 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PSMD12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-67340873-G-T is Benign according to our data. Variant chr17-67340873-G-T is described in ClinVar as [Benign]. Clinvar id is 1879380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 725 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PSMD12	NM_002816.5 linkuse as main transcript	c.1341C>A	p.Ala447=	synonymous_variant	11/11	ENST00000356126.8
PSMD12	NM_174871.4 linkuse as main transcript	c.1281C>A	p.Ala427=	synonymous_variant	10/10
PSMD12	NM_001316341.2 linkuse as main transcript	c.1164C>A	p.Ala388=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD12	ENST00000356126.8 linkuse as main transcript	c.1341C>A	p.Ala447=	synonymous_variant	11/11	1	NM_002816.5	P1	O00232-1
PSMD12	ENST00000584008.5 linkuse as main transcript	c.*1496C>A		3_prime_UTR_variant, NMD_transcript_variant	13/13	1
PSMD12	ENST00000357146.4 linkuse as main transcript	c.1281C>A	p.Ala427=	synonymous_variant	10/10	2			O00232-2

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

725

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00868

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00469

AC:

1055

AN:

224956

Hom.:

AF XY:

0.00461

AC XY:

564

AN XY:

122268

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00406

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000482

Gnomad FIN exome

AF:

0.00225

Gnomad NFE exome

AF:

0.00841

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00834

AC:

11962

AN:

1433852

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

5811

AN XY:

713132

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.00460

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000883

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00610

GnomAD4 genome

AF:

0.00477

AC:

725

AN:

151890

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

320

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00155

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00162

Gnomad4 NFE

AF:

0.00868

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00721

Hom.:

Bravo

AF:

0.00493

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PSMD12: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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