NM_005600.3:c.203C>T

Variant names:

• chr1-161119238-C-T
• NM_005600.3:c.203C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005600.3(NIT1):​c.203C>T​(p.Ala68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NIT1 NM_005600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28842527).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005600.3. 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
	NIT1	NM_005600.3	MANE Select	c.203C>T	p.Ala68Val	missense	Exon 3 of 7	NP_005591.1	Q86X76-1
	NIT1	NM_001185093.2		c.158C>T	p.Ala53Val	missense	Exon 2 of 6	NP_001172022.1	Q86X76-4
	NIT1	NM_001185094.2		c.95C>T	p.Ala32Val	missense	Exon 3 of 7	NP_001172023.1	Q86X76-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIT1	ENST00000368009.7	TSL:1 MANE Select	c.203C>T	p.Ala68Val	missense	Exon 3 of 7	ENSP00000356988.2	Q86X76-1
	NIT1	ENST00000368008.5	TSL:1	c.203C>T	p.Ala68Val	missense	Exon 3 of 7	ENSP00000356987.1	Q86X76-5
	NIT1	ENST00000496861.5	TSL:1	n.767C>T		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0033
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.36	N
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.13	B
Vest4		0.49
MutPred		0.54		Gain of methylation at K65 (P = 0.0902)
MVP		0.77
MPC		0.027
ClinPred		0.29	T
GERP RS		5.1
Varity_R		0.081
gMVP		0.50
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr1-161089028;