8-123416895-C-G

Position:

• chr8-123416895-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018024.3(NTAQ1):​c.46C>G​(p.Pro16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NTAQ1 NM_018024.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21872166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTAQ1	NM_018024.3	c.46C>G	p.Pro16Ala	missense_variant	1/6	ENST00000287387.7	NP_060494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTAQ1	ENST00000287387.7	c.46C>G	p.Pro16Ala	missense_variant	1/6	1	NM_018024.3	ENSP00000287387.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1374156 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 677380

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2024

The c.46C>G (p.P16A) alteration is located in exon 1 (coding exon 1) of the WDYHV1 gene. This alteration results from a C to G substitution at nucleotide position 46, causing the proline (P) at amino acid position 16 to be replaced by an alanine (A). 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	Benign	0.12
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.077
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	D;.
Vest4		0.14
MutPred		0.34		Loss of glycosylation at P16 (P = 0.0103);Loss of glycosylation at P16 (P = 0.0103);
MVP		0.54
MPC		0.33
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-124429135;