1-161120113-C-T

Variant names:

• chr1-161120113-C-T
• rs148079618
• NM_005600.3:c.598C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005600.3(NIT1):​c.598C>T​(p.Leu200Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NIT1 NM_005600.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=2.88 with no splicing effect.

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.598C>T	p.Leu200Leu	synonymous	Exon 6 of 7	NP_005591.1	Q86X76-1
	NIT1	NM_001185093.2		c.553C>T	p.Leu185Leu	synonymous	Exon 5 of 6	NP_001172022.1	Q86X76-4
	NIT1	NM_001185094.2		c.490C>T	p.Leu164Leu	synonymous	Exon 6 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.598C>T	p.Leu200Leu	synonymous	Exon 6 of 7	ENSP00000356988.2	Q86X76-1
	NIT1	ENST00000368008.5	TSL:1	c.598C>T	p.Leu200Leu	synonymous	Exon 6 of 7	ENSP00000356987.1	Q86X76-5
	NIT1	ENST00000496861.5	TSL:1	n.1162C>T		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251340 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461796 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		2.9
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs148079618; hg19: chr1-161089903;