Variant chr19-16731220-G-A 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_001007525.5(NWD1):c.23G>A(p.Arg8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000717 in 1,534,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

NWD1
NM_001007525.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219

Variant links:

Genes affected

NWD1 (HGNC:27619): (NACHT and WD repeat domain containing 1) The protein encoded by this gene is thought to be a cytosolic protein and predicted to contain a NACHT domain and multiple WD40 repeats. Increased expression of this gene was observed in some prostate cancer cell lines. Knocking down expression of this gene results in decreased androgen receptor protein levels, indicating that this gene may be important in modulating androgen receptor activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

NWD1 links:

NWD1 (HGNC:):

NWD1 links:

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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=0.0048218966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NWD1	NM_001007525.5 linkuse as main transcript	c.23G>A	p.Arg8Lys	missense_variant	3/19	ENST00000524140.7	NP_001007526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NWD1	ENST00000524140.7 linkuse as main transcript	c.23G>A	p.Arg8Lys	missense_variant	3/19	1	NM_001007525.5	ENSP00000428579.2		Q149M9-3

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000271

AC:

AN:

140100

Hom.:

AF XY:

0.000290

AC XY:

AN XY:

75806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00289

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000708

GnomAD4 exome

AF:

0.0000694

AC:

AN:

1382464

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

682310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000308

Gnomad4 ASJ exome

AF:

0.00231

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.000276

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000311

AC:

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

May 31, 2022

The c.23G>A (p.R8K) alteration is located in exon 3 (coding exon 1) of the NWD1 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the arginine (R) at amino acid position 8 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.7

DANN

Benign

0.90

DEOGEN2

Benign

0.00032

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.35

.;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;.;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.48

N;N;N;N

REVEL

Benign

0.054

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.069

MutPred

0.34

Gain of methylation at R8 (P = 0.0037);Gain of methylation at R8 (P = 0.0037);Gain of methylation at R8 (P = 0.0037);Gain of methylation at R8 (P = 0.0037);

MVP

0.048

MPC

0.19

ClinPred

0.021

GERP RS

1.3

Varity_R

0.089

gMVP

0.12

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