Variant 8-123437300-G-C 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_018024.3(NTAQ1):c.474G>C(p.Glu158Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

NTAQ1
NM_018024.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.755

Variant links:

Genes affected

NTAQ1 (HGNC:25490): (N-terminal glutamine amidase 1) Predicted to enable protein-N-terminal glutamine amidohydrolase activity. Predicted to be involved in cellular protein modification process. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NTAQ1 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=0.027399749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTAQ1	NM_018024.3 linkuse as main transcript	c.474G>C	p.Glu158Asp	missense_variant	5/6	ENST00000287387.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTAQ1	ENST00000287387.7 linkuse as main transcript	c.474G>C	p.Glu158Asp	missense_variant	5/6	1	NM_018024.3	P1	Q96HA8-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000275

AC:

AN:

251178

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000186

AC:

272

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

137

AN XY:

727198

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:

0.00

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.000298

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000164

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

Dec 06, 2023

The c.474G>C (p.E158D) alteration is located in exon 5 (coding exon 5) of the WDYHV1 gene. This alteration results from a G to C substitution at nucleotide position 474, causing the glutamic acid (E) at amino acid position 158 to be replaced by an aspartic acid (D). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.;.;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.97

D;.;D;D;D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.027

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.;.;.;.

MutationTaster

Benign

0.84

D;D;D;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

N;N;.;.;N;N

REVEL

Benign

0.032

Sift

Uncertain

0.015

D;D;.;.;D;D

Sift4G

Benign

0.26

T;T;.;.;T;T

Polyphen

0.072

B;.;.;.;.;.

Vest4

0.25

MutPred

0.38

Loss of glycosylation at P160 (P = 0.1224);.;.;.;Loss of glycosylation at P160 (P = 0.1224);.;

MVP

0.16

MPC

0.053

ClinPred

0.045

GERP RS

-1.7

Varity_R

0.74

gMVP

0.46

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