Variant 8-123428022-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001283024.1(NTAQ1):c.2T>C(p.Met1?) variant causes a start lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,590,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

NTAQ1
NM_001283024.1 start_lost, splice_region

Scores

Splicing: ADA: 0.00007974

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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:

NTAQ1 (HGNC:):

NTAQ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTAQ1	NM_018024.3 linkuse as main transcript	c.182T>C	p.Met61Thr	missense_variant, splice_region_variant	2/6	ENST00000287387.7	NP_060494.1	Q96HA8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTAQ1	ENST00000287387.7 linkuse as main transcript	c.182T>C	p.Met61Thr	missense_variant, splice_region_variant	2/6	1	NM_018024.3	ENSP00000287387.2		Q96HA8-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.0000509

AC:

AN:

235596

Hom.:

AF XY:

0.0000628

AC XY:

AN XY:

127298

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:

0.00

Gnomad NFE exome

AF:

0.0000913

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1438724

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

715728

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000509

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.000105

AC:

AN:

151734

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74090

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.000178

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

Nov 15, 2024

The c.182T>C (p.M61T) alteration is located in exon 2 (coding exon 2) of the WDYHV1 gene. This alteration results from a T to C substitution at nucleotide position 182, causing the methionine (M) at amino acid position 61 to be replaced by a threonine (T). 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

0.36

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0046

T;.;.;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

T;.;D;D;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.069

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.38

N;.;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.61

N;N;.;.;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;D;.;.;T

Sift4G

Benign

1.0

T;D;.;.;T

Polyphen

0.099

B;.;.;.;.

Vest4

0.38

MVP

0.099

MPC

0.31

ClinPred

0.048

GERP RS

3.0

Varity_R

0.18

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000080

dbscSNV1_RF

Benign

0.020

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