rs6470147

Positions:

• chr8-123436564-T-A
• chr8-123436564-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018024.3(NTAQ1):​c.346T>A​(p.Phe116Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,613,040 control chromosomes in the GnomAD database, including 105,543 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (10088 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95455 hom.)
• Consequence: NTAQ1 NM_018024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5219064E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTAQ1	NM_018024.3	c.346T>A	p.Phe116Ile	missense_variant	4/6	ENST00000287387.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTAQ1	ENST00000287387.7	c.346T>A	p.Phe116Ile	missense_variant	4/6	1	NM_018024.3	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55044 AN: 151852 Hom.: 10083 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.382 AC: 96005 AN: 251244 Hom.: 18761 AF XY: 0.380 AC XY: 51595 AN XY: 135800

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.358 AC: 523478 AN: 1461070 Hom.: 95455 Cov.: 40 AF XY: 0.360 AC XY: 261710 AN XY: 726870

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.362 AC: 55074 AN: 151970 Hom.: 10088 Cov.: 32 AF XY: 0.366 AC XY: 27201 AN XY: 74254

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.372

Alfa AF: 0.354 Hom.: 7453

Bravo AF: 0.366

TwinsUK AF: 0.350 AC: 1298

ALSPAC AF: 0.341 AC: 1316

ESP6500AA AF: 0.363 AC: 1600

ESP6500EA AF: 0.352 AC: 3029

ExAC AF: 0.380 AC: 46104

Asia WGS AF: 0.472 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.060	T;.;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.0082
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;.;T;T;T
MetaRNN	Benign	0.00045	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.;.;.;.
MutationTaster	Benign	0.018	P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D;D;.;.;D
REVEL	Benign	0.045
Sift	Benign	0.085	T;D;.;.;T
Sift4G	Benign	0.42	T;T;.;.;T
Polyphen		0.092	B;.;.;.;.
Vest4		0.29
MPC		0.19
ClinPred		0.040	T
GERP RS		4.4
Varity_R		0.30
gMVP		0.56

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

Other links and lift over

dbSNP: rs6470147; hg19: chr8-124448804; COSMIC: COSV54873861;