1-161119519-C-T

Variant names:

• chr1-161119519-C-T
• rs1186842058
• NM_005600.3:c.364C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005600.3(NIT1):​c.364C>T​(p.Leu122Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIT1 NM_005600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

NIT1 (HGNC:7828): (nitrilase 1) This gene encodes a member of the nitrilase protein family with homology to bacterial and plant nitrilases, enzymes that cleave nitriles and organic amides to the corresponding carboxylic acids plus ammonia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIT1	NM_005600.3	c.364C>T	p.Leu122Phe	missense_variant	Exon 4 of 7	ENST00000368009.7	NP_005591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIT1	ENST00000368009.7	c.364C>T	p.Leu122Phe	missense_variant	Exon 4 of 7	1	NM_005600.3	ENSP00000356988.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.364C>T (p.L122F) alteration is located in exon 4 (coding exon 4) of the NIT1 gene. This alteration results from a C to T substitution at nucleotide position 364, causing the leucine (L) at amino acid position 122 to be replaced by a phenylalanine (F). 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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	1.9	L;.;.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.012	.;D;D;.
Polyphen		0.87	P;P;.;.
Vest4		0.62
MutPred		0.68		Loss of stability (P = 0.1567);.;.;Loss of stability (P = 0.1567);
MVP		0.89
MPC		0.050
ClinPred		0.74	D
GERP RS		2.6
Varity_R		0.14
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs1186842058; hg19: chr1-161089309;