NM_001394862.1:c.792A>G

Variant names:

• chr12-11267457-T-C
• rs369202988
• NM_001394862.1:c.792A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BP6_Moderate BP7 BS2_Supporting

The NM_001394862.1(PRB3):​c.792A>G​(p.Pro264Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,461,926 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00081 (7 hom.)
• Consequence: PRB3 NM_001394862.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 12-11267457-T-C is Benign according to our data. Variant chr12-11267457-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2642708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.038 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.792A>G	p.Pro264Pro	synonymous	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.666A>G	p.Pro222Pro	synonymous	Exon 4 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.792A>G	p.Pro264Pro	synonymous	Exon 3 of 4	ENSP00000442626.2	Q04118

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 72 AN: 119070 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000417

Gnomad ASJ AF: 0.000678

Gnomad EAS AF: 0.000976

Gnomad SAS AF: 0.00219

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000671

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00124 AC: 288 AN: 232864 AF XY: 0.00122

Gnomad AFR exome AF: 0.000341

Gnomad AMR exome AF: 0.000859

Gnomad ASJ exome AF: 0.000212

Gnomad EAS exome AF: 0.00352

Gnomad FIN exome AF: 0.00187

Gnomad NFE exome AF: 0.000921

Gnomad OTH exome AF: 0.00192

GnomAD4 exome AF: 0.000807 AC: 1083 AN: 1342734 Hom.: 7 Cov.: 44 AF XY: 0.000846 AC XY: 562 AN XY: 664434

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

African (AFR) AF: 0.000291 AC: 9 AN: 30904

American (AMR) AF: 0.000679 AC: 28 AN: 41214

Ashkenazi Jewish (ASJ) AF: 0.000928 AC: 21 AN: 22632

East Asian (EAS) AF: 0.00421 AC: 126 AN: 29952

South Asian (SAS) AF: 0.00289 AC: 226 AN: 78334

European-Finnish (FIN) AF: 0.00131 AC: 59 AN: 44914

Middle Eastern (MID) AF: 0.00122 AC: 6 AN: 4928

European-Non Finnish (NFE) AF: 0.000520 AC: 539 AN: 1036144

Other (OTH) AF: 0.00128 AC: 69 AN: 53712

⚠️ 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 AF: 0.000612 AC: 73 AN: 119192 Hom.: 0 Cov.: 17 AF XY: 0.000664 AC XY: 38 AN XY: 57248

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

African (AFR) AF: 0.000282 AC: 9 AN: 31910

American (AMR) AF: 0.000417 AC: 5 AN: 11998

Ashkenazi Jewish (ASJ) AF: 0.000678 AC: 2 AN: 2950

East Asian (EAS) AF: 0.000978 AC: 3 AN: 3068

South Asian (SAS) AF: 0.00218 AC: 6 AN: 2750

European-Finnish (FIN) AF: 0.00137 AC: 10 AN: 7290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000671 AC: 38 AN: 56650

Other (OTH) AF: 0.00 AC: 0 AN: 1580

⚠️ 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: 0.000429 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.038
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: rs369202988; hg19: chr12-11420391; COSMIC: COSV54393257; COSMIC: COSV54393257;