NM_018024.3:c.346T>A

Variant names:

• chr8-123436564-T-A
• rs6470147
• NM_018024.3:c.346T>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018024.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAQ1	NM_018024.3	MANE Select	c.346T>A	p.Phe116Ile	missense	Exon 4 of 6	NP_060494.1
	NTAQ1	NM_001283024.1		c.166T>A	p.Phe56Ile	missense	Exon 4 of 6	NP_001269953.1
	NTAQ1	NM_001283027.1		c.142T>A	p.Phe48Ile	missense	Exon 5 of 7	NP_001269956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAQ1	ENST00000287387.7	TSL:1 MANE Select	c.346T>A	p.Phe116Ile	missense	Exon 4 of 6	ENSP00000287387.2
	NTAQ1	ENST00000523356.1	TSL:3	c.346T>A	p.Phe116Ile	missense	Exon 4 of 7	ENSP00000428615.1
	NTAQ1	ENST00000650311.1		c.166T>A	p.Phe56Ile	missense	Exon 4 of 7	ENSP00000497747.1

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

GnomAD2 exomes AF: 0.382 AC: 96005 AN: 251244 AF XY: 0.380

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 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

African (AFR) AF: 0.350 AC: 11700 AN: 33458

American (AMR) AF: 0.411 AC: 18362 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10195 AN: 26120

East Asian (EAS) AF: 0.575 AC: 22789 AN: 39656

South Asian (SAS) AF: 0.405 AC: 34892 AN: 86222

European-Finnish (FIN) AF: 0.375 AC: 20007 AN: 53394

Middle Eastern (MID) AF: 0.340 AC: 1961 AN: 5768

European-Non Finnish (NFE) AF: 0.343 AC: 381266 AN: 1111386

Other (OTH) AF: 0.370 AC: 22306 AN: 60360

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

African (AFR) AF: 0.351 AC: 14558 AN: 41454

American (AMR) AF: 0.398 AC: 6071 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2882 AN: 5150

South Asian (SAS) AF: 0.414 AC: 1996 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3784 AN: 10536

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23377 AN: 67976

Other (OTH) AF: 0.372 AC: 784 AN: 2110

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 v4.9

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
MetaRNN	Benign	0.00045	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.045
Sift	Benign	0.085	T
Sift4G	Benign	0.42	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
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

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