Genetic Variant ATIC:c.815-102T>A (chr2-215333248-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004044.7(ATIC):c.815-102T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.503

Publications

29 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ATIC links:

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ACMG classification

Classification was made for transcript

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=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.815-102T>A		intron_variant	Intron 8 of 15	ENST00000236959.14	NP_004035.2	P31939-1V9HWH7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATIC	ENST00000236959.14 link	c.815-102T>A	intron_variant	Intron 8 of 15	1	NM_004044.7	ENSP00000236959.9	P31939-1
ATIC	ENST00000435675.5 link	c.812-102T>A	intron_variant	Intron 7 of 14	2		ENSP00000415935.1	P31939-2
ATIC	ENST00000427397.5 link	n.*708-102T>A	intron_variant	Intron 7 of 8	5		ENSP00000394317.1	F2Z3E8
ATIC	ENST00000443953.5 link	n.*912-102T>A	intron_variant	Intron 8 of 15	2		ENSP00000406792.1	F2Z3E8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

772396

Hom.:

AF XY:

0.00

AC XY:

AN XY:

408294

African (AFR)

AF:

0.00

AC:

AN:

19658

American (AMR)

AF:

0.00

AC:

AN:

38400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21236

East Asian (EAS)

AF:

0.00

AC:

AN:

35500

South Asian (SAS)

AF:

0.00

AC:

AN:

69492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

495732

Other (OTH)

AF:

0.00

AC:

AN:

37482

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.43

(source)

DANN

Benign

0.79

PhyloP100

-0.50

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over