rs200940772

Variant names:

• chr12-11267839-C-G
• rs200940772
• NM_001394862.1:c.410G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-11267839-C-G
• chr12-11267839-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394862.1(PRB3):​c.410G>C​(p.Arg137Pro) 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. R137H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 4)
  • Exomes 𝑓: 0.0000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 8 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059655458).

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.410G>C	p.Arg137Pro	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.410G>C	p.Arg137Pro	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.410G>C	p.Arg137Pro	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.417G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000294 AC: 1 AN: 339992 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 185788

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

African (AFR) AF: 0.00 AC: 0 AN: 8204

American (AMR) AF: 0.00 AC: 0 AN: 15338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8054

East Asian (EAS) AF: 0.00 AC: 0 AN: 25638

South Asian (SAS) AF: 0.00 AC: 0 AN: 39364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1168

European-Non Finnish (NFE) AF: 0.00000523 AC: 1 AN: 191046

Other (OTH) AF: 0.00 AC: 0 AN: 17198

⚠️ 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 Cov.: 4

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	2.6
DANN	Benign	0.40
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00099	N
M_CAP	Benign	0.00043	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.96	T
PhyloP100		-3.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.061
Sift4G	Benign	1.0	T
Vest4		0.12
MutPred		0.43		Gain of catalytic residue at P135 (P = 2e-04)
MVP		0.030
MPC		0.48
ClinPred		0.070	T
GERP RS		-1.4
gMVP		0.21
Mutation Taster		=99/1	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: rs200940772; hg19: chr12-11420773;