rs373731645

Variant names:

• chr3-100339146-C-G
• rs373731645
• NM_020202.5:c.67C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-100339146-C-G
• chr3-100339146-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.67C>G​(p.Arg23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R23C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIT2 NM_020202.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 3 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, 0.842

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.67C>G	p.Arg23Gly	missense	Exon 2 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.67C>G	p.Arg23Gly	missense	Exon 2 of 10	ENSP00000377696.3	Q9NQR4
	NIT2	ENST00000465368.5	TSL:1	n.120C>G		non_coding_transcript_exon	Exon 2 of 9
	NIT2	ENST00000497785.1	TSL:5	c.346C>G	p.Arg116Gly	missense	Exon 2 of 6	ENSP00000419189.1	H7C579

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.72
Sift	Benign	0.043	D
Sift4G	Benign	0.11	T
Polyphen		0.43	B
Vest4		0.79
MutPred		0.60		Loss of MoRF binding (P = 0.1218)
MVP		0.63
MPC		0.27
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.78
gMVP		0.77
Mutation Taster		=46/54	disease causing

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: rs373731645; hg19: chr3-100057990; COSMIC: COSV67630327;