Variant 13-28662352-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015932.6(POMP):c.4-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,290,764 control chromosomes in the GnomAD database, including 97,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14121 hom., cov: 32)

Exomes 𝑓: 0.38 ( 83705 hom. )

Consequence

POMP
NM_015932.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0280

Variant links:

Genes affected

POMP (HGNC:20330): (proteasome maturation protein) The protein encoded by this gene is a molecular chaperone that binds 20S preproteasome components and is essential for 20S proteasome formation. The 20S proteasome is the proteolytically active component of the 26S proteasome complex. The encoded protein is degraded before the maturation of the 20S proteasome is complete. A variant in the 5' UTR of this gene has been associated with KLICK syndrome, a rare skin disorder.[provided by RefSeq, Aug 2010]

POMP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 13-28662352-C-T is Benign according to our data. Variant chr13-28662352-C-T is described in ClinVar as [Benign]. Clinvar id is 1288406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMP	NM_015932.6 linkuse as main transcript	c.4-58C>T		intron_variant		ENST00000380842.5	NP_057016.1	Q9Y244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMP	ENST00000380842.5 linkuse as main transcript	c.4-58C>T		intron_variant		1	NM_015932.6	ENSP00000370222.4		Q9Y244

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64109

AN:

151766

Hom.:

14094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.371

GnomAD4 exome

AF:

0.375

AC:

427205

AN:

1138880

Hom.:

83705

AF XY:

0.373

AC XY:

216923

AN XY:

581102

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.584

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.498

Gnomad4 SAS exome

AF:

0.410

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.423

AC:

64188

AN:

151884

Hom.:

14121

Cov.:

AF XY:

0.428

AC XY:

31768

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.476

Gnomad4 ASJ

AF:

0.265

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.401

Hom.:

1562

Bravo

AF:

0.433

Asia WGS

AF:

0.514

AC:

1781

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

DANN

Benign

0.18

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