2-215312084-T-C

Variant names:

• chr2-215312084-T-C
• rs4535042
• NM_004044.7:c.-59T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004044.7(ATIC):​c.-59T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,980 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: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ATIC NM_004044.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 19 publications found

Genes affected

ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

ATIC Gene-Disease associations (from GenCC):

• AICA-ribosiduria

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

LOC124907975 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004044.7. 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
	ATIC	NM_004044.7	MANE Select	c.-59T>C		5_prime_UTR	Exon 1 of 16	NP_004035.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.-59T>C		5_prime_UTR	Exon 1 of 16	ENSP00000236959.9	P31939-1
	ATIC	ENST00000957330.1		c.-59T>C		5_prime_UTR	Exon 1 of 16	ENSP00000627389.1
	ATIC	ENST00000939851.1		c.-59T>C		5_prime_UTR	Exon 1 of 16	ENSP00000609910.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376980 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 679562

African (AFR) AF: 0.00 AC: 0 AN: 30752

American (AMR) AF: 0.00 AC: 0 AN: 35402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24936

East Asian (EAS) AF: 0.00 AC: 0 AN: 35294

South Asian (SAS) AF: 0.00 AC: 0 AN: 78322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076218

Other (OTH) AF: 0.00 AC: 0 AN: 57508

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.55
PhyloP100		-0.14
PromoterAI		0.45	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4535042; hg19: chr2-216176807;