Variant rs141872658 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004044.7(ATIC):c.1234G>A(p.Glu412Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000591 in 1,613,988 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

ATIC
NM_004044.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.96

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 links:

ATIC (HGNC:):

ATIC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009370267).

BP6

Variant 2-215344785-G-A is Benign according to our data. Variant chr2-215344785-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 376861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATIC	NM_004044.7 linkuse as main transcript	c.1234G>A	p.Glu412Lys	missense_variant	13/16	ENST00000236959.14	NP_004035.2	P31939-1V9HWH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14 linkuse as main transcript	c.1234G>A	p.Glu412Lys	missense_variant	13/16	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

507

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000887

AC:

223

AN:

251374

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000306

AC:

448

AN:

1461752

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

193

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00332

AC:

506

AN:

152236

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

258

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000519

Hom.:

Bravo

AF:

0.00355

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00109

AC:

132

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ATIC: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 28, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.50

Sift

Benign

0.13

T;T

Sift4G

Benign

0.087

T;T

Polyphen

0.65

P;.

Vest4

0.65

MVP

0.82

MPC

0.059

ClinPred

0.036

GERP RS

5.9

Varity_R

0.54

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over