chr13-28659201-C-T

Variant names:

• chr13-28659201-C-T
• rs756047393
• NM_015932.6:c.3+14C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_015932.6(POMP):​c.3+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,588,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: POMP NM_015932.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.134
• Publications: 0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000289569 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 13-28659201-C-T is Benign according to our data. Variant chr13-28659201-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1646846.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015932.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMP	NM_015932.6	MANE Select	c.3+14C>T		intron	N/A	NP_057016.1	Q9Y244

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMP	ENST00000380842.5	TSL:1 MANE Select	c.3+14C>T		intron	N/A	ENSP00000370222.4	Q9Y244
	POMP	ENST00000697718.1		c.3+14C>T		intron	N/A	ENSP00000513416.1	A0A8V8TLM3
	POMP	ENST00000883662.1		c.3+14C>T		intron	N/A	ENSP00000553721.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000341 AC: 7 AN: 205506 AF XY: 0.0000181

Gnomad AFR exome AF: 0.000499

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000216 AC: 31 AN: 1436542 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 10 AN XY: 712314

African (AFR) AF: 0.000884 AC: 29 AN: 32796

American (AMR) AF: 0.00 AC: 0 AN: 41240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.00 AC: 0 AN: 37972

South Asian (SAS) AF: 0.00 AC: 0 AN: 82556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1100796

Other (OTH) AF: 0.0000169 AC: 1 AN: 59328

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74362

African (AFR) AF: 0.000845 AC: 35 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000242

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.95
PhyloP100		-0.13
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756047393; hg19: chr13-29233338;