chr12-11267905-G-T

Variant names:

• chr12-11267905-G-T
• NM_001394862.1:c.344C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394862.1(PRB3):​c.344C>A​(p.Pro115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 11)
• Consequence: PRB3 NM_001394862.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.192
• Publications: 0 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.106824934).

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.344C>A	p.Pro115His	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.344C>A	p.Pro115His	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.344C>A	p.Pro115His	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.351C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0014	N
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.19
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift4G	Pathogenic	0.0010	D
Vest4		0.25
MutPred		0.30		Gain of catalytic residue at P113 (P = 0.0028)
MVP		0.061
MPC		0.38
ClinPred		0.21	T
GERP RS		-1.0
gMVP		0.19
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

hg19: chr12-11420839;