12-11267400-AG-AGG

Variant names:

• chr12-11267400-A-AG
• rs3842295
• NM_001394862.1:c.848dupC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001394862.1(PRB3):​c.848dupC​(p.His284SerfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• 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
• Publications: 6 publications found

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

Our verdict: Uncertain_significance. The variant received 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 VariationId is 13734.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394862.1. 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
	PRB3	NM_001394862.1	MANE Select	c.848dupC	p.His284SerfsTer14	frameshift	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.722dupC	p.His242SerfsTer14	frameshift	Exon 4 of 5	NP_006240.4	A0A0G2JNB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB3	ENST00000538488.3	TSL:5 MANE Select	c.848dupC	p.His284SerfsTer14	frameshift	Exon 3 of 4	ENSP00000442626.2	Q04118

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 5001 AN: 121030 Hom.: 703 Cov.: 27

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

African (AFR) AF: 0.216 AC: 7060 AN: 32624

American (AMR) AF: 0.0114 AC: 507 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 347 AN: 25812

East Asian (EAS) AF: 0.175 AC: 6192 AN: 35324

South Asian (SAS) AF: 0.0192 AC: 1616 AN: 84242

European-Finnish (FIN) AF: 0.0107 AC: 561 AN: 52574

Middle Eastern (MID) AF: 0.0159 AC: 90 AN: 5678

European-Non Finnish (NFE) AF: 0.00283 AC: 3134 AN: 1107676

Other (OTH) AF: 0.0235 AC: 1399 AN: 59656

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

African (AFR) AF: 0.143 AC: 4031 AN: 28138

American (AMR) AF: 0.0131 AC: 169 AN: 12874

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 37 AN: 3016

East Asian (EAS) AF: 0.111 AC: 314 AN: 2824

South Asian (SAS) AF: 0.0148 AC: 49 AN: 3314

European-Finnish (FIN) AF: 0.00791 AC: 66 AN: 8344

Middle Eastern (MID) AF: 0.00410 AC: 1 AN: 244

European-Non Finnish (NFE) AF: 0.00460 AC: 275 AN: 59772

Other (OTH) AF: 0.0389 AC: 67 AN: 1724

Alfa AF: 0.0688 Hom.: 5

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	PRB3M(NULL) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.045
Mutation Taster		=142/58	polymorphism

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

Other links and lift over

dbSNP: rs3842295; hg19: chr12-11420333;