8-123438124-G-T

Variant names:

• chr8-123438124-G-T
• rs3765212
• NM_018024.3:c.508+790G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018024.3(NTAQ1):​c.508+790G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 698,838 control chromosomes in the GnomAD database, including 49,259 homozygotes. In-silico tool predicts 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 (10109 hom., cov: 32)
  • Exomes 𝑓: 0.37 (39150 hom.)
• Consequence: NTAQ1 NM_018024.3 intron
• Scores: Splicing: ADA: 0.00002399
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 13 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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 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.508+790G>T		intron	N/A	NP_060494.1
	NTAQ1	NM_001283024.1		c.328+790G>T		intron	N/A	NP_001269953.1
	NTAQ1	NM_001283027.1		c.304+790G>T		intron	N/A	NP_001269956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAQ1	ENST00000287387.7	TSL:1 MANE Select	c.508+790G>T		intron	N/A	ENSP00000287387.2
	NTAQ1	ENST00000523356.1	TSL:3	c.509-10G>T		intron	N/A	ENSP00000428615.1
	NTAQ1	ENST00000650311.1		c.328+790G>T		intron	N/A	ENSP00000497747.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55099 AN: 151920 Hom.: 10104 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.389 AC: 49061 AN: 126140 AF XY: 0.387

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.387

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.372 AC: 203566 AN: 546800 Hom.: 39150 Cov.: 0 AF XY: 0.374 AC XY: 110693 AN XY: 296062

African (AFR) AF: 0.350 AC: 5479 AN: 15672

American (AMR) AF: 0.405 AC: 13834 AN: 34154

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 7776 AN: 19894

East Asian (EAS) AF: 0.577 AC: 18458 AN: 31986

South Asian (SAS) AF: 0.404 AC: 25122 AN: 62250

European-Finnish (FIN) AF: 0.374 AC: 12363 AN: 33098

Middle Eastern (MID) AF: 0.349 AC: 1414 AN: 4052

European-Non Finnish (NFE) AF: 0.342 AC: 107844 AN: 315248

Other (OTH) AF: 0.370 AC: 11276 AN: 30446

GnomAD4 genome AF: 0.363 AC: 55129 AN: 152038 Hom.: 10109 Cov.: 32 AF XY: 0.367 AC XY: 27239 AN XY: 74318

African (AFR) AF: 0.351 AC: 14568 AN: 41466

American (AMR) AF: 0.398 AC: 6072 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2900 AN: 5170

South Asian (SAS) AF: 0.414 AC: 1996 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3809 AN: 10556

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23379 AN: 67984

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.359 Hom.: 2311

Bravo AF: 0.366

Asia WGS AF: 0.472 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
DANN	Benign	0.63
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3765212; hg19: chr8-124450364; COSMIC: COSV107283161;