13-28662209-A-T

Position:

• chr13-28662209-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015932.6(POMP):​c.4-201A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,942 control chromosomes in the GnomAD database, including 18,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.47 (18472 hom., cov: 32)
• Consequence: POMP NM_015932.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-28662209-A-T is Benign according to our data. Variant chr13-28662209-A-T is described in ClinVar as [Benign]. Clinvar id is 1255316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMP	NM_015932.6	c.4-201A>T		intron_variant		ENST00000380842.5	NP_057016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMP	ENST00000380842.5	c.4-201A>T		intron_variant		1	NM_015932.6	ENSP00000370222.4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71356 AN: 151824 Hom.: 18435 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71451 AN: 151942 Hom.: 18472 Cov.: 32 AF XY: 0.474 AC XY: 35192 AN XY: 74252

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.409

Alfa AF: 0.429 Hom.: 1869

Bravo AF: 0.488

Asia WGS AF: 0.525 AC: 1821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
CADD	Benign	1.3
DANN	Benign	0.62

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: rs1340816; hg19: chr13-29236346;