12-11267692-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001394862.1(PRB3):c.557C>A(p.Pro186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 12)
  • Exomes 𝑓: 0.00015 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005709827).
• BP6: Variant 12-11267692-G-T is Benign according to our data. Variant chr12-11267692-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642709.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRB3	NM_001394862.1	c.557C>A	p.Pro186Gln	missense_variant	3/4	ENST00000538488.3
LOC107987435	XR_007063209.1	n.761-9778G>T		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5	c.557C>A	p.Pro186Gln	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRB3	ENST00000538488.3	c.557C>A	p.Pro186Gln	missense_variant	3/4	5	NM_001394862.1	P1

Frequencies

GnomAD3 genomes AF: 0.000540 AC: 49 AN: 90718 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.000527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.000456

Gnomad FIN AF: 0.00125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000274

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000455 AC: 108 AN: 237158 Hom.: 1 AF XY: 0.000356 AC XY: 46 AN XY: 129110

Gnomad AFR exome AF: 0.000220

Gnomad AMR exome AF: 0.0000945

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00515

Gnomad SAS exome AF: 0.0000692

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.0000642

Gnomad OTH exome AF: 0.000175

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000145 AC: 203 AN: 1398750 Hom.: 2 Cov.: 33 AF XY: 0.000145 AC XY: 101 AN XY: 695574

Gnomad4 AFR exome AF: 0.000168

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.000167

Gnomad4 EAS exome AF: 0.00270

Gnomad4 SAS exome AF: 0.0000872

Gnomad4 FIN exome AF: 0.000269

Gnomad4 NFE exome AF: 0.0000420

Gnomad4 OTH exome AF: 0.000261

GnomAD4 genome AF: 0.000529 AC: 48 AN: 90754 Hom.: 0 Cov.: 12 AF XY: 0.000703 AC XY: 31 AN XY: 44098

Gnomad4 AFR AF: 0.000526

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00301

Gnomad4 SAS AF: 0.000457

Gnomad4 FIN AF: 0.00125

Gnomad4 NFE AF: 0.000274

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000670 AC: 8

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PRB3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	3.7
Dann	Benign	0.23
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0081	N
MetaRNN	Benign	0.0057	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.032
Sift4G	Uncertain	0.024	D;D
Vest4		0.19
MVP		0.048
MPC		0.31
ClinPred		0.022	T
GERP RS		1.2
gMVP		0.46

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: rs113564509; hg19: chr12-11420626; COSMIC: COSV54388818; COSMIC: COSV54388818;