Genetic Variant PRB1:p.Gly114Glu (chr12-11353363-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000500254.6(PRB1):c.341G>A(p.Gly114Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,365,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0000072 ( 1 hom. )

Consequence

PRB1
ENST00000500254.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.759

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101558626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRB1	NR_160307.2 link	n.778G>A		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
PRB1	ENST00000500254.6 link	c.341G>A	p.Gly114Glu	missense_variant	Exon 4 of 5	1	ENSP00000420826.2	A0A4W8X8U3
PRB1	ENST00000545626.5 link	c.314-33G>A		intron_variant	Intron 3 of 4	1	ENSP00000444249.1	G3V1R1
PRB1	ENST00000240636.10 link	n.*284G>A		non_coding_transcript_exon_variant	Exon 3 of 4	1	ENSP00000485971.1	A0A0D9SET1
PRB1	ENST00000240636.10 link	n.*284G>A		3_prime_UTR_variant	Exon 3 of 4	1	ENSP00000485971.1	A0A0D9SET1

Frequencies

GnomAD3 genomes

AF:

0.0000262

AC:

AN:

114348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000860

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:

0.0000348

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

245332

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000671

GnomAD4 exome

AF:

0.00000719

AC:

AN:

1251512

Hom.:

Cov.:

AF XY:

0.00000807

AC XY:

AN XY:

619464

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000541

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000513

Gnomad4 OTH exome

AF:

0.0000399

GnomAD4 genome

AF:

0.0000262

AC:

AN:

114348

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

54984

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000860

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000348

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000846

Hom.:

ExAC

AF:

0.00000908

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.740G>A (p.G247E) 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 740, causing the glycine (G) at amino acid position 247 to be replaced by a glutamic acid (E). 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

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.41

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00088

M_CAP

Benign

0.00081

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.015

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.31

T;T

Vest4

0.16

MutPred

0.34

Gain of catalytic residue at P111 (P = 5e-04);.;

MVP

0.17

MPC

0.067

ClinPred

0.14

GERP RS

-2.4

gMVP

0.022

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over