chr1-161119909-C-T

Variant names:

• chr1-161119909-C-T
• rs1315826766
• NM_005600.3:c.548C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69

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 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
NIT1	NM_005600.3	c.548C>T	p.Pro183Leu	missense_variant	Exon 5 of 7	ENST00000368009.7	NP_005591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIT1	ENST00000368009.7	c.548C>T	p.Pro183Leu	missense_variant	Exon 5 of 7	1	NM_005600.3	ENSP00000356988.2

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

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

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

Other links and lift over

dbSNP: rs1315826766; hg19: chr1-161089699;