Genetic Variant PRB1:p.Gly156Val (chr12-11353237-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000500254.6(PRB1):c.467G>T(p.Gly156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,588,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G156D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PRB1
ENST00000500254.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

Publications

0 publications found

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]

PRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.15185094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500254.6. 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
	PRB1	NR_160307.2		n.904G>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRB1	ENST00000500254.6	TSL:1	c.467G>T	p.Gly156Val	missense	Exon 4 of 5	ENSP00000420826.2	A0A4W8X8U3
PRB1	ENST00000545626.5	TSL:1	c.407G>T	p.Gly136Val	missense	Exon 4 of 5	ENSP00000444249.1	G3V1R1
PRB1	ENST00000240636.10	TSL:1	n.*410G>T		non_coding_transcript_exon	Exon 3 of 4	ENSP00000485971.1	A0A0D9SET1

Frequencies

GnomAD3 genomes

AF:

0.0000367

AC:

AN:

136274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

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:

0.00000805

AC:

AN:

248482

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.000132

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:

0.00000344

AC:

AN:

1452456

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722622

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

32354

American (AMR)

AF:

0.00

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105584

Other (OTH)

AF:

0.00

AC:

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000440

AC:

AN:

136368

Hom.:

Cov.:

AF XY:

0.0000452

AC XY:

AN XY:

66384

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33354

American (AMR)

AF:

0.00

AC:

AN:

13960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3328

East Asian (EAS)

AF:

0.00

AC:

AN:

4908

South Asian (SAS)

AF:

0.00

AC:

AN:

4294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64020

Other (OTH)

AF:

0.00

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.045

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.0011

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PhyloP100

0.14

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.2

REVEL

Benign

0.059

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

0.98

Vest4

0.13

MutPred

0.38

Gain of catalytic residue at P151 (P = 6e-04)

MVP

0.18

MPC

0.066

ClinPred

0.22

GERP RS

0.034

gMVP

0.033

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over