13-28662352-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0280

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]

ACMG classification

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	UniProt
POMP	NM_015932.6	c.4-58C>T		intron_variant		ENST00000380842.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMP	ENST00000380842.5	c.4-58C>T		intron_variant		1	NM_015932.6	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64109 AN: 151766 Hom.: 14094 Cov.: 32

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

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.: 32 AF XY: 0.428 AC XY: 31768 AN XY: 74206

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs1340815; hg19: chr13-29236489; COSMIC: COSV66481987;