12-11267400-A-AG

Position:

• chr12-11267400-A-AG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_001394862.1(PRB3):​c.848dupC​(p.His284fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.041 (704 hom., cov: 27)
  • Exomes 𝑓: 0.014 (2714 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.0450

Genes affected

PRB3 (HGNC:9339): (proline rich protein BstNI subfamily 3) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats have been identified. The reference genome encodes the "Long" allele. The protein isoforms encoded by this gene are recognized as the "first line of oral defense" against the detrimental effects of polyphenols in the diet and pathogen infections. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, Nov 2015]

LOC107987435 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant 12-11267400-A-AG is Pathogenic according to our data. Variant chr12-11267400-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 13734.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB3	NM_001394862.1	c.848dupC	p.His284fs	frameshift_variant	3/4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5	c.722dupC	p.His242fs	frameshift_variant	4/5		NP_006240.4
LOC107987435	XR_007063209.1	n.761-10068dupG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3	c.848dupC	p.His284fs	frameshift_variant	3/4	5	NM_001394862.1	ENSP00000442626.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5001 AN: 121030 Hom.: 703 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0123

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0148

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.00388

Gnomad NFE AF: 0.00458

Gnomad OTH AF: 0.0394

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0144 AC: 20906 AN: 1448072 Hom.: 2714 Cov.: 34 AF XY: 0.0139 AC XY: 10004 AN XY: 719796

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.0134

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.0235

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0414 AC: 5010 AN: 121116 Hom.: 704 Cov.: 27 AF XY: 0.0419 AC XY: 2451 AN XY: 58544

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.0123

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0148

Gnomad4 FIN AF: 0.00791

Gnomad4 NFE AF: 0.00460

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0688 Hom.: 5

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PRB3M(NULL) Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1990

- -

Computational scores

Source: dbNSFP v4.3

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: rs3842295; hg19: chr12-11420333;