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GeneBe

12-11267457-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001394862.1(PRB3):c.792A>G(p.Pro264=) 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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-11267457-T-C is Benign according to our data. Variant chr12-11267457-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642708.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.038 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRB3NM_001394862.1 linkuse as main transcriptc.792A>G p.Pro264= synonymous_variant 3/4 ENST00000538488.3
LOC107987435XR_007063209.1 linkuse as main transcriptn.761-10013T>C intron_variant, non_coding_transcript_variant
PRB3NM_006249.5 linkuse as main transcriptc.666A>G p.Pro222= synonymous_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRB3ENST00000538488.3 linkuse as main transcriptc.792A>G p.Pro264= synonymous_variant 3/45 NM_001394862.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000605
AC:
72
AN:
119070
Hom.:
0
Cov.:
17
show subpopulations
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
GnomAD3 exomes
AF:
0.00124
AC:
288
AN:
232864
Hom.:
3
AF XY:
0.00122
AC XY:
153
AN XY:
125666
show subpopulations
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 SAS exome
AF:
0.00184
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
show subpopulations
Gnomad4 AFR exome
AF:
0.000291
Gnomad4 AMR exome
AF:
0.000679
Gnomad4 ASJ exome
AF:
0.000928
Gnomad4 EAS exome
AF:
0.00421
Gnomad4 SAS exome
AF:
0.00289
Gnomad4 FIN exome
AF:
0.00131
Gnomad4 NFE exome
AF:
0.000520
Gnomad4 OTH exome
AF:
0.00128
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000612
AC:
73
AN:
119192
Hom.:
0
Cov.:
17
AF XY:
0.000664
AC XY:
38
AN XY:
57248
show subpopulations
Gnomad4 AFR
AF:
0.000282
Gnomad4 AMR
AF:
0.000417
Gnomad4 ASJ
AF:
0.000678
Gnomad4 EAS
AF:
0.000978
Gnomad4 SAS
AF:
0.00218
Gnomad4 FIN
AF:
0.00137
Gnomad4 NFE
AF:
0.000671
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000429
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2022PRB3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
Cadd
Benign
2.9
Dann
Benign
0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369202988; hg19: chr12-11420391; COSMIC: COSV54393257; COSMIC: COSV54393257; API