Variant 13-28659206-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015932.6(POMP):c.3+19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,587,438 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 28 hom. )

Consequence

POMP
NM_015932.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0820

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 13-28659206-G-C is Benign according to our data. Variant chr13-28659206-G-C is described in ClinVar as [Benign]. Clinvar id is 1601637.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00147 (224/152356) while in subpopulation EAS AF= 0.0336 (174/5186). AF 95% confidence interval is 0.0295. There are 8 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMP	NM_015932.6 linkuse as main transcript	c.3+19G>C		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.3+19G>C		intron_variant		1	NM_015932.6	ENSP00000370222.4		Q9Y244

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

223

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00273

AC:

552

AN:

202078

Hom.:

AF XY:

0.00257

AC XY:

280

AN XY:

108754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000268

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0332

Gnomad SAS exome

AF:

0.000728

Gnomad FIN exome

AF:

0.00104

Gnomad NFE exome

AF:

0.0000564

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00121

AC:

1738

AN:

1435082

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

854

AN XY:

711442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0355

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.0000509

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152356

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.00184

Asia WGS

AF:

0.0150

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.9

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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