12-11353279-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000500254.6(PRB1):​c.425G>A​(p.Arg142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,573,254 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 21)
Exomes 𝑓: 0.000082 ( 5 hom. )

Consequence

PRB1
ENST00000500254.6 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.260
Variant links:
Genes affected
PRB1 (HGNC:9337): (proline rich protein BstNI subfamily 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.124393165).
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRB1NR_160307.2 linkn.862G>A non_coding_transcript_exon_variant Exon 3 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRB1ENST00000500254.6 linkc.425G>A p.Arg142Gln missense_variant Exon 4 of 5 1 ENSP00000420826.2 A0A4W8X8U3
PRB1ENST00000545626.5 linkc.365G>A p.Arg122Gln missense_variant Exon 4 of 5 1 ENSP00000444249.1 G3V1R1
PRB1ENST00000240636.10 linkn.*368G>A non_coding_transcript_exon_variant Exon 3 of 4 1 ENSP00000485971.1 A0A0D9SET1
PRB1ENST00000240636.10 linkn.*368G>A 3_prime_UTR_variant Exon 3 of 4 1 ENSP00000485971.1 A0A0D9SET1

Frequencies

GnomAD3 genomes
AF:
0.0000147
AC:
2
AN:
135908
Hom.:
0
Cov.:
21
show subpopulations
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:
0.0000312
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000761
AC:
19
AN:
249594
Hom.:
1
AF XY:
0.0000740
AC XY:
10
AN XY:
135056
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.000598
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000619
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000821
AC:
118
AN:
1437346
Hom.:
5
Cov.:
89
AF XY:
0.0000699
AC XY:
50
AN XY:
715442
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000927
Gnomad4 ASJ exome
AF:
0.000396
Gnomad4 EAS exome
AF:
0.0000519
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000857
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.0000147
AC:
2
AN:
135908
Hom.:
0
Cov.:
21
AF XY:
0.0000151
AC XY:
1
AN XY:
66038
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000312
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000119
Hom.:
0
ExAC
AF:
0.0000579
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.824G>A (p.R275Q) alteration is located in exon 3 (coding exon 3) of the PRB1 gene. This alteration results from a G to A substitution at nucleotide position 824, causing the arginine (R) at amino acid position 275 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
7.3
DANN
Benign
0.46
DEOGEN2
Benign
0.0030
.;.;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0019
N
M_CAP
Benign
0.00070
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.87
N;N;.
REVEL
Benign
0.10
Sift
Benign
0.38
T;T;.
Sift4G
Benign
0.39
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.16
MutPred
0.43
.;Gain of catalytic residue at P144 (P = 0.0028);.;
MVP
0.030
MPC
0.061
ClinPred
0.031
T
GERP RS
-1.0
gMVP
0.032

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: rs201751674; hg19: chr12-11506213; COSMIC: COSV53703215; API