chr1-161119909-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005600.3(NIT1):​c.548C>T​(p.Pro183Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NIT1
NM_005600.3 missense

Scores

4
13
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIT1NM_005600.3 linkc.548C>T p.Pro183Leu missense_variant Exon 5 of 7 ENST00000368009.7 NP_005591.1 Q86X76-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIT1ENST00000368009.7 linkc.548C>T p.Pro183Leu missense_variant Exon 5 of 7 1 NM_005600.3 ENSP00000356988.2 Q86X76-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250556
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135422
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.548C>T (p.P183L) alteration is located in exon 5 (coding exon 5) of the NIT1 gene. This alteration results from a C to T substitution at nucleotide position 548, causing the proline (P) at amino acid position 183 to be replaced by a leucine (L). 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
0.18
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;.;.;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Uncertain
0.70
D;D;D;D
MetaSVM
Uncertain
0.72
D
MutationAssessor
Pathogenic
3.7
H;.;.;H
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-5.7
D;D;D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.022
.;D;D;.
Polyphen
0.57
P;P;.;.
Vest4
0.52
MutPred
0.60
Loss of glycosylation at S180 (P = 0.0483);.;.;Loss of glycosylation at S180 (P = 0.0483);
MVP
0.84
MPC
0.14
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.53
gMVP
0.79

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: rs1315826766; hg19: chr1-161089699; API