rs885219

Positions:

• chr13-28672069-A-G

Variant summary

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

The ENST00000380842.5(POMP):​c.265-270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,090 control chromosomes in the GnomAD database, including 11,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (11066 hom., cov: 32)
• Consequence: POMP ENST00000380842.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789

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=-0.91).
• BP6: Variant 13-28672069-A-G is Benign according to our data. Variant chr13-28672069-A-G is described in ClinVar as [Benign]. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMP	NM_015932.6	c.265-270A>G		intron_variant		ENST00000380842.5	NP_057016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMP	ENST00000380842.5	c.265-270A>G		intron_variant		1	NM_015932.6	ENSP00000370222	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48996 AN: 151972 Hom.: 11030 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.323 AC: 49097 AN: 152090 Hom.: 11066 Cov.: 32 AF XY: 0.327 AC XY: 24299 AN XY: 74346

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.270

Alfa AF: 0.177 Hom.: 6001

Bravo AF: 0.343

Asia WGS AF: 0.305 AC: 1057 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs885219; hg19: chr13-29246206;