Variant 2-215325297-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004044.7(ATIC):c.347C>G(p.Thr116Ser) variant causes a missense change. The variant allele was found at a frequency of 0.319 in 1,610,906 control chromosomes in the GnomAD database, including 86,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6016 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80046 hom. )

Consequence

ATIC
NM_004044.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017181039).

BP6

Variant 2-215325297-C-G is Benign according to our data. Variant chr2-215325297-C-G is described in ClinVar as [Benign]. Clinvar id is 801893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7 linkuse as main transcript	c.347C>G	p.Thr116Ser	missense_variant	5/16	ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14 linkuse as main transcript	c.347C>G	p.Thr116Ser	missense_variant	5/16	1	NM_004044.7	P1	P31939-1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39259

AN:

151858

Hom.:

6007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.325

AC:

81828

AN:

251410

Hom.:

14359

AF XY:

0.338

AC XY:

45939

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0877

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.294

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.325

AC:

474575

AN:

1458932

Hom.:

80046

Cov.:

AF XY:

0.331

AC XY:

240355

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.0778

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.327

GnomAD4 genome

AF:

0.259

AC:

39289

AN:

151974

Hom.:

6016

Cov.:

AF XY:

0.259

AC XY:

19235

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0917

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.472

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.313

Hom.:

2565

Bravo

AF:

0.253

TwinsUK

AF:

0.325

AC:

1205

ALSPAC

AF:

0.328

AC:

1263

ESP6500AA

AF:

0.0962

AC:

424

ESP6500EA

AF:

0.324

AC:

2786

ExAC

AF:

0.323

AC:

39268

Asia WGS

AF:

0.388

AC:

1346

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.334

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

AICA-ribosiduria

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

ATIC-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;.;.

Eigen

Benign

0.028

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.6e-9

P;P;P

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.11

MutPred

0.24

Gain of disorder (P = 0.0286);.;.;

MPC

0.050

ClinPred

0.033

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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