chr12-11268104-G-C

Variant names:

• chr12-11268104-G-C
• rs71455367
• NM_001394862.1:c.145C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM2 PM5 BP4_Strong

The NM_001394862.1(PRB3):​c.145C>G​(p.Arg49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R49C) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 5 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr12-11268104-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 13733.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.0345982).

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.145C>G	p.Arg49Gly	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.145C>G	p.Arg49Gly	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.145C>G	p.Arg49Gly	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.152C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143676 Hom.: 0 Cov.: 28

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249400 AF XY: 0.00

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457174 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 724810

African (AFR) AF: 0.0000306 AC: 1 AN: 32726

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109324

Other (OTH) AF: 0.0000166 AC: 1 AN: 60104

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143676 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 69974

African (AFR) AF: 0.00 AC: 0 AN: 37950

American (AMR) AF: 0.00 AC: 0 AN: 14460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 4782

South Asian (SAS) AF: 0.00 AC: 0 AN: 4316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65780

Other (OTH) AF: 0.00 AC: 0 AN: 1928

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.60
DANN	Benign	0.28
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00027	N
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.018
Sift4G	Benign	0.47	T
Vest4		0.072
MutPred		0.39		Gain of catalytic residue at P51 (P = 0)
MVP		0.040
MPC		0.43
ClinPred		0.054	T
GERP RS		-0.37
gMVP		0.17
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: rs71455367; hg19: chr12-11421038;