Variant 19-16749190-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001347994.1(NWD1):c.-71A>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 0.00457 in 1,613,412 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 95 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 107 hom. )

Consequence

NWD1
NM_001347994.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.185

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029247105).

BP6

Variant 19-16749190-A-T is Benign according to our data. Variant chr19-16749190-A-T is described in ClinVar as [Benign]. Clinvar id is 782326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NWD1	NM_001007525.5 linkuse as main transcript	c.548A>T	p.Gln183Leu	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.548A>T	p.Gln183Leu	missense_variant	6/19	1	NM_001007525.5	ENSP00000428579.2		Q149M9-3

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3084

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.00662

AC:

1658

AN:

250434

Hom.:

AF XY:

0.00588

AC XY:

796

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00190

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000716

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00294

AC:

4289

AN:

1461184

Hom.:

107

Cov.:

AF XY:

0.00288

AC XY:

2092

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.0691

Gnomad4 AMR exome

AF:

0.00502

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.00673

GnomAD4 genome

AF:

0.0203

AC:

3089

AN:

152228

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1502

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0667

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.0238

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0633

AC:

279

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00807

AC:

980

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.7

DANN

Benign

0.74

DEOGEN2

Benign

0.021

.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.51

.;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M;M

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.011

Sift

Benign

0.046

D;D;D;D

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.11

MVP

0.030

MPC

0.14

ClinPred

0.017

GERP RS

-7.3

Varity_R

0.11

gMVP

0.21

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