3-100339146-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020202.5(NIT2):​c.67C>T​(p.Arg23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NIT2
NM_020202.5 missense

Scores

7
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIT2NM_020202.5 linkc.67C>T p.Arg23Cys missense_variant Exon 2 of 10 ENST00000394140.9 NP_064587.1 Q9NQR4V9HW91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIT2ENST00000394140.9 linkc.67C>T p.Arg23Cys missense_variant Exon 2 of 10 1 NM_020202.5 ENSP00000377696.3 Q9NQR4

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000942
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251482
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461824
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.000942
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.000223
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000988
AC:
12
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.67C>T (p.R23C) alteration is located in exon 2 (coding exon 2) of the NIT2 gene. This alteration results from a C to T substitution at nucleotide position 67, causing the arginine (R) at amino acid position 23 to be replaced by a cysteine (C). 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
0.26
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.35
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.45
T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.93
D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Uncertain
0.33
D
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-6.4
D
REVEL
Pathogenic
0.85
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.021
D
Polyphen
1.0
D
Vest4
0.75
MVP
0.73
MPC
0.74
ClinPred
0.66
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.69
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373731645; hg19: chr3-100057990; COSMIC: COSV67630724; API