Variant 19-16749183-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001347994.1(NWD1):c.-78C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,612,846 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

NWD1
NM_001347994.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.260

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062392056).

BP6

Variant 19-16749183-C-T is Benign according to our data. Variant chr19-16749183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649516.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NWD1	NM_001007525.5 linkuse as main transcript	c.541C>T	p.Arg181Trp	missense_variant	6/19	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.541C>T	p.Arg181Trp	missense_variant	6/19	1	NM_001007525.5	ENSP00000428579.2		Q149M9-3

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00192

AC:

479

AN:

249902

Hom.:

AF XY:

0.00199

AC XY:

269

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00704

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00192

AC:

2806

AN:

1460688

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1387

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000538

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00697

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152158

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.00182

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00192

AC:

233

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

NWD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.3

DANN

Benign

0.95

DEOGEN2

Benign

0.044

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.019

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.99

D;.;D;.

Vest4

0.10

MVP

0.030

MPC

0.15

ClinPred

0.032

GERP RS

-3.8

Varity_R

0.041

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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