rs751318008

Variant names:

• chr3-100348880-C-G
• rs751318008
• NM_020202.5:c.583C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-100348880-C-G
• chr3-100348880-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020202.5(NIT2):​c.583C>G​(p.Arg195Gly) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R195Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIT2 NM_020202.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003202
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

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.583C>G	p.Arg195Gly	missense splice_region	Exon 7 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.583C>G	p.Arg195Gly	missense splice_region	Exon 7 of 10	ENSP00000377696.3	Q9NQR4
	NIT2	ENST00000465368.5	TSL:1	n.1138C>G		splice_region non_coding_transcript_exon	Exon 6 of 9
	NIT2	ENST00000867930.1		c.508C>G	p.Arg170Gly	missense splice_region	Exon 6 of 9	ENSP00000537989.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	4.4	H
PhyloP100		0.057
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.84		Loss of stability (P = 0.027)
MVP		0.72
MPC		0.73
ClinPred		1.0	D
GERP RS		2.7
Varity_R		0.98
gMVP		0.96
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.092
SpliceAI score (max)		0.010		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: rs751318008; hg19: chr3-100067724;