Variant rs147327994 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031485.4(GRWD1):c.593G>A(p.Arg198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

GRWD1
NM_031485.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

GRWD1 (HGNC:21270): (glutamate rich WD repeat containing 1) This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012]

GRWD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022213042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRWD1	NM_031485.4 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/7	ENST00000253237.10	NP_113673.3	Q9BQ67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRWD1	ENST00000253237.10 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/7	1	NM_031485.4	ENSP00000253237.4		Q9BQ67
GRWD1	ENST00000598711.1 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/6	3		ENSP00000468943.1		M0QX71

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251366

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000151

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.593G>A (p.R198Q) alteration is located in exon 4 (coding exon 4) of the GRWD1 gene. This alteration results from a G to A substitution at nucleotide position 593, causing the arginine (R) at amino acid position 198 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Malignant tumor of prostate

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.39

N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.54

N;.

REVEL

Benign

0.053

Sift

Benign

0.38

T;.

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;.

Vest4

0.15

MVP

0.77

MPC

0.39

ClinPred

0.026

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.16

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