Genetic Variant PRR11:p.Arg106Cys (chr17-59185476-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 NM_018304.4(PRR11):c.316C>T(p.Arg106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000807 in 1,573,894 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

PRR11
NM_018304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360

Variant links:

Genes affected

PRR11 (HGNC:25619): (proline rich 11) Involved in regulation of cell cycle. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRR11 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=0.10079056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR11	NM_018304.4 link	c.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 10	ENST00000262293.9	NP_060774.2	Q96HE9D2SNZ4
PRR11	XM_024450828.2 link	c.316C>T	p.Arg106Cys	missense_variant	Exon 5 of 11		XP_024306596.1
PRR11	XM_047436387.1 link	c.316C>T	p.Arg106Cys	missense_variant	Exon 5 of 11		XP_047292343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR11	ENST00000262293.9 link	c.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 10	1	NM_018304.4	ENSP00000262293.5		Q96HE9

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

136552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000827

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000727

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000484

Gnomad OTH

AF:

0.000552

GnomAD3 exomes

AF:

0.000129

AC:

AN:

247324

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

133924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000821

AC:

118

AN:

1437342

Hom.:

Cov.:

AF XY:

0.0000741

AC XY:

AN XY:

715590

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.000165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000957

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.0000794

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000659

AC:

AN:

136552

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

66660

show subpopulations

Gnomad4 AFR

AF:

0.0000827

Gnomad4 AMR

AF:

0.0000727

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000102

Gnomad4 NFE

AF:

0.0000484

Gnomad4 OTH

AF:

0.000552

Alfa

AF:

0.0000465

Hom.:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316C>T (p.R106C) alteration is located in exon 4 (coding exon 3) of the PRR11 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the arginine (R) at amino acid position 106 to be replaced by a cysteine (C). 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.15

T;T;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;L

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.0

D;.;.;.

REVEL

Benign

0.089

Sift

Uncertain

0.0010

D;.;.;.

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.055

B;.;.;B

Vest4

0.35

MutPred

0.48

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);

MVP

0.31

MPC

0.27

ClinPred

0.25

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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