rs71455367

chr12-11268104-G-Achr12-11268104-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5 BP4

The NM_001394862.1(PRB3):c.145C>T(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,601,000 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 28)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.57

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 0 ACMG points.

• PP5: Variant 12-11268104-G-A is Pathogenic according to our data. Variant chr12-11268104-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 13733.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.0053963363).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRB3	NM_001394862.1	c.145C>T	p.Arg49Cys	missense_variant	3/4	ENST00000538488.3
LOC107987435	XR_007063209.1	n.761-9366G>A		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5	c.145C>T	p.Arg49Cys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRB3	ENST00000538488.3	c.145C>T	p.Arg49Cys	missense_variant	3/4	5	NM_001394862.1	P1
PRB3	ENST00000539835.1	n.152C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 155 AN: 143688 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.000158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00145

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000463

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000851

Gnomad OTH AF: 0.00519

GnomAD3 exomes AF: 0.00135 AC: 336 AN: 249400 Hom.: 1 AF XY: 0.00132 AC XY: 178 AN XY: 135256

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000850

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00103 AC: 1496 AN: 1457180 Hom.: 3 Cov.: 41 AF XY: 0.00103 AC XY: 746 AN XY: 724816

Gnomad4 AFR exome AF: 0.0000611

Gnomad4 AMR exome AF: 0.000920

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000830

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.00108 AC: 155 AN: 143820 Hom.: 1 Cov.: 28 AF XY: 0.000884 AC XY: 62 AN XY: 70110

Gnomad4 AFR AF: 0.000158

Gnomad4 AMR AF: 0.00145

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000463

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000851

Gnomad4 OTH AF: 0.00512

Alfa AF: 0.00108 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00175 AC: 15

ExAC AF: 0.00115 AC: 139

EpiCase AF: 0.00109

EpiControl AF: 0.00143

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PRB3S(CYS) Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1990

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	12
Dann	Benign	0.87
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0010	N
M_CAP	Benign	0.00098	T
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.041
Sift4G	Uncertain	0.054	T;T
Vest4		0.25
MVP		0.030
MPC		0.45
ClinPred		0.014	T
GERP RS		-0.37
gMVP		0.19

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: rs71455367; hg19: chr12-11421038; COSMIC: COSV54389308;