rs756067624

Variant names:

• chr3-100345649-C-A
• rs756067624
• NM_020202.5:c.401C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-100345649-C-A
• chr3-100345649-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020202.5(NIT2):​c.401C>A​(p.Pro134Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P134L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NIT2 NM_020202.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.90
• Publications: 0 publications found

Genes affected

NIT2 (HGNC:29878): (nitrilase family member 2) Enables omega-amidase activity. Involved in asparagine metabolic process; glutamine metabolic process; and oxaloacetate metabolic process. Located in centrosome and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIT2	NM_020202.5	MANE Select	c.401C>A	p.Pro134Gln	missense	Exon 5 of 10	NP_064587.1	Q9NQR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIT2	ENST00000394140.9	TSL:1 MANE Select	c.401C>A	p.Pro134Gln	missense	Exon 5 of 10	ENSP00000377696.3	Q9NQR4
	NIT2	ENST00000465368.5	TSL:1	n.454C>A		non_coding_transcript_exon	Exon 5 of 9
	NIT2	ENST00000497785.1	TSL:5	c.680C>A	p.Pro227Gln	missense	Exon 5 of 6	ENSP00000419189.1	H7C579

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460256 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726510

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110790

Other (OTH) AF: 0.0000166 AC: 1 AN: 60330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		6.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.66		Gain of solvent accessibility (P = 0.1045)
MVP		0.92
MPC		0.30
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.83
gMVP		0.83
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs756067624; hg19: chr3-100064493;