Variant chr2-161367778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_005805.6(PSMD14):c.121-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,612,860 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 16 hom. )

Consequence

PSMD14
NM_005805.6 splice_region, intron

Scores

Splicing: ADA: 0.0006472

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

PSMD14 (HGNC:16889): (proteasome 26S subunit, non-ATPase 14) This gene encodes a component of the 26S proteasome. The 26S proteasome is a large multiprotein complex that catalyzes the degradation of ubiquitinated intracellular proteins. The encoded protein is a component of the 19S regulatory cap complex of the 26S proteasome and mediates substrate deubiquitination. A pseudogene of this gene is also located on the long arm of chromosome 2. [provided by RefSeq, Feb 2012]

PSMD14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 2-161367778-C-A is Benign according to our data. Variant chr2-161367778-C-A is described in ClinVar as [Benign]. Clinvar id is 718397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 305 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD14	NM_005805.6 linkuse as main transcript	c.121-6C>A		splice_region_variant, intron_variant		ENST00000409682.8	NP_005796.1	O00487A0A140VKF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD14	ENST00000409682.8 linkuse as main transcript	c.121-6C>A		splice_region_variant, intron_variant		1	NM_005805.6	ENSP00000386541.3		O00487
PSMD14	ENST00000437630.1 linkuse as main transcript	c.121-6C>A		splice_region_variant, intron_variant		5		ENSP00000399311.1		C9JW37

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00302

AC:

747

AN:

247506

Hom.:

AF XY:

0.00370

AC XY:

497

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.00298

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.00222

AC:

3238

AN:

1460576

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

1914

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.00335

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00200

AC:

305

AN:

152284

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00306

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00065

dbscSNV1_RF

Benign

0.21

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