chr17-44010885-T-C

Variant names:

• chr17-44010885-T-C
• rs228776
• ENST00000906978.1:c.*2284T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000906978.1(NAGS):​c.*2284T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,220 control chromosomes in the GnomAD database, including 66,895 homozygotes. 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: 𝑓 0.94 (66895 hom., cov: 31)
• Consequence: NAGS ENST00000906978.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 4 publications found

Genes affected

NAGS (HGNC:17996): (N-acetylglutamate synthase) The N-acetylglutamate synthase gene encodes a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme-A. NAG is a cofactor of carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in mammals. This gene may regulate ureagenesis by altering NAG availability and, thereby, CPSI activity. Deficiencies in N-acetylglutamate synthase have been associated with hyperammonemia. [provided by RefSeq, Jul 2008]

NAGS Gene-Disease associations (from GenCC):

• hyperammonemia due to N-acetylglutamate synthase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000906978.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGS	ENST00000906978.1		c.*2284T>C		3_prime_UTR	Exon 7 of 7	ENSP00000577037.1
	NAGS	ENST00000906977.1		c.*2284T>C		3_prime_UTR	Exon 7 of 7	ENSP00000577036.1

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142535 AN: 152102 Hom.: 66838 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.952

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.937 AC: 142650 AN: 152220 Hom.: 66895 Cov.: 31 AF XY: 0.940 AC XY: 69982 AN XY: 74434

African (AFR) AF: 0.903 AC: 37468 AN: 41494

American (AMR) AF: 0.960 AC: 14690 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3325 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.989 AC: 4775 AN: 4830

European-Finnish (FIN) AF: 0.950 AC: 10078 AN: 10610

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.941 AC: 64016 AN: 68020

Other (OTH) AF: 0.952 AC: 2013 AN: 2114

Alfa AF: 0.937 Hom.: 7772

Bravo AF: 0.935

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.59
DANN	Benign	0.56
PhyloP100		-0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs228776; hg19: chr17-42088253;