12-11267755-G-C

Variant names:

• chr12-11267755-G-C
• rs199658095
• NM_001394862.1:c.494C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394862.1(PRB3):​c.494C>G​(p.Pro165Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P165Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000052 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12003881).

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.494C>G	p.Pro165Arg	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.494C>G	p.Pro165Arg	missense	Exon 3 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.494C>G	p.Pro165Arg	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.*25C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000521 AC: 1 AN: 19184 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

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: 0.0000905

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000155 AC: 3 AN: 193480 AF XY: 0.00000945

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000647

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.000227

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000140 AC: 16 AN: 1145930 Hom.: 1 Cov.: 22 AF XY: 0.0000122 AC XY: 7 AN XY: 571784

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000466 AC: 1 AN: 21482

American (AMR) AF: 0.0000419 AC: 1 AN: 23878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16334

East Asian (EAS) AF: 0.0000569 AC: 2 AN: 35154

South Asian (SAS) AF: 0.0000325 AC: 2 AN: 61464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3056

European-Non Finnish (NFE) AF: 0.0000101 AC: 9 AN: 891698

Other (OTH) AF: 0.0000216 AC: 1 AN: 46376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000521 AC: 1 AN: 19204 Hom.: 0 Cov.: 5 AF XY: 0.000105 AC XY: 1 AN XY: 9552

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3054

American (AMR) AF: 0.00 AC: 0 AN: 1858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 624

East Asian (EAS) AF: 0.00 AC: 0 AN: 930

South Asian (SAS) AF: 0.00 AC: 0 AN: 288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 20

European-Non Finnish (NFE) AF: 0.0000905 AC: 1 AN: 11048

Other (OTH) AF: 0.00 AC: 0 AN: 262

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.74
DANN	Benign	0.037
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
M_CAP	Benign	0.00051	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.081
Sift4G	Benign	0.14	T
Vest4		0.18
MutPred		0.34		Gain of catalytic residue at P166 (P = 0)
MVP		0.048
MPC		0.35
ClinPred		0.13	T
GERP RS		0.14
gMVP		0.54
Mutation Taster		=100/0	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: rs199658095; hg19: chr12-11420689;