rs1288775

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001321015.2(GATM):c.-58A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,613,390 control chromosomes in the GnomAD database, including 107,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 20539 hom., cov: 32)

Exomes 𝑓: 0.31 ( 87388 hom. )

Consequence

GATM
NM_001321015.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

GATM (HGNC:4175): (glycine amidinotransferase) This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]

GATM 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=5.735975E-7).

BP6

Variant 15-45369480-T-A is Benign according to our data. Variant chr15-45369480-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 129138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45369480-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATM	NM_001482.3 link	c.330A>T	p.Gln110His	missense_variant	Exon 3 of 9	ENST00000396659.8	NP_001473.1	P50440-1A0A140VK19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000396659.8 link	c.330A>T	p.Gln110His	missense_variant	Exon 3 of 9	1	NM_001482.3	ENSP00000379895.3		P50440-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70125

AN:

152004

Hom.:

20476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.786

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.439

GnomAD3 exomes

AF:

0.421

AC:

105856

AN:

251160

Hom.:

27832

AF XY:

0.400

AC XY:

54283

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.793

Gnomad AMR exome

AF:

0.652

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.830

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.314

AC:

459387

AN:

1461268

Hom.:

87388

Cov.:

AF XY:

0.314

AC XY:

228182

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.804

Gnomad4 AMR exome

AF:

0.635

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.847

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.309

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.462

AC:

70246

AN:

152122

Hom.:

20539

Cov.:

AF XY:

0.466

AC XY:

34627

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.786

Gnomad4 AMR

AF:

0.516

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.836

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.288

Hom.:

5456

Bravo

AF:

0.497

TwinsUK

AF:

0.254

AC:

943

ALSPAC

AF:

0.259

AC:

997

ESP6500AA

AF:

0.763

AC:

3354

ESP6500EA

AF:

0.267

AC:

2297

ExAC

AF:

0.418

AC:

50750

Asia WGS

AF:

0.629

AC:

2183

AN:

3478

EpiCase

AF:

0.277

EpiControl

AF:

0.274

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 76% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 71. Only high quality variants are reported. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 21, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arginine:glycine amidinotransferase deficiency

Benign:5

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 29, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Fanconi renotubular syndrome 1

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.040

T;T;T

MetaRNN

Benign

5.7e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.63

N;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

1.3

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.54

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.14

MutPred

0.12

Gain of disorder (P = 0.0912);Gain of disorder (P = 0.0912);.;

MPC

0.64

ClinPred

0.00063

GERP RS

3.5

Varity_R

0.054

gMVP

0.58

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