chr13-28672069-A-G

Variant names:

• chr13-28672069-A-G
• rs885219
• NM_015932.6:c.265-270A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015932.6(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 NM_015932.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar as Benign. Clinvar id is 1264933.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-28672069-A-G is described in CliVar 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 rank	MANE	Protein	UniProt
POMP	NM_015932.6	c.265-270A>G		intron_variant	Intron 4 of 5	ENST00000380842.5	NP_057016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMP	ENST00000380842.5	c.265-270A>G		intron_variant	Intron 4 of 5	1	NM_015932.6	ENSP00000370222.4

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

African (AFR) AF: 0.635 AC: 26313 AN: 41460

American (AMR) AF: 0.326 AC: 4985 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1513 AN: 5182

South Asian (SAS) AF: 0.180 AC: 870 AN: 4828

European-Finnish (FIN) AF: 0.306 AC: 3235 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10963 AN: 68000

Other (OTH) AF: 0.270 AC: 571 AN: 2114

Alfa AF: 0.210 Hom.: 15422

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs885219; hg19: chr13-29246206;