Variant 17-59195352-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018304.4(PRR11):c.766C>T(p.Arg256Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,460 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000046 ( 2 hom. )

Consequence

PRR11
NM_018304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04324013).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR11	NM_018304.4 linkuse as main transcript	c.766C>T	p.Arg256Trp	missense_variant	7/10	ENST00000262293.9	NP_060774.2	Q96HE9D2SNZ4
PRR11	XM_024450828.2 linkuse as main transcript	c.766C>T	p.Arg256Trp	missense_variant	8/11		XP_024306596.1
PRR11	XM_047436387.1 linkuse as main transcript	c.766C>T	p.Arg256Trp	missense_variant	8/11		XP_047292343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRR11	ENST00000262293.9 linkuse as main transcript	c.766C>T	p.Arg256Trp	missense_variant	7/10	1	NM_018304.4	ENSP00000262293.5	Q96HE9
PRR11	ENST00000614081.1 linkuse as main transcript	c.766C>T	p.Arg256Trp	missense_variant	7/11	1		ENSP00000481852.1	Q96HE9
PRR11	ENST00000580177.5 linkuse as main transcript	n.766C>T		non_coding_transcript_exon_variant	7/11	1		ENSP00000463733.1	Q96HE9
PRR11	ENST00000578542.5 linkuse as main transcript	n.766C>T		non_coding_transcript_exon_variant	7/11	5		ENSP00000464171.1	Q96HE9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152084

Hom.:

Cov.:

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:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251356

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74288

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:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.766C>T (p.R256W) alteration is located in exon 7 (coding exon 6) of the PRR11 gene. This alteration results from a C to T substitution at nucleotide position 766, causing the arginine (R) at amino acid position 256 to be replaced by a tryptophan (W). 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

0.090

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-4.9

D;.

REVEL

Benign

0.028

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.023

D;D

Polyphen

0.12

B;B

Vest4

0.24

MutPred

0.27

Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);

MVP

0.51

MPC

0.17

ClinPred

0.24

GERP RS

1.9

Varity_R

0.10

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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