Variant 12-120446488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_176818.3(GATC):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,606,746 control chromosomes in the GnomAD database, including 3,074 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.045 ( 261 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2813 hom. )

Consequence

GATC
NM_176818.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.479

Variant links:

Genes affected

GATC (HGNC:25068): (glutamyl-tRNA amidotransferase subunit C) Enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 42. [provided by Alliance of Genome Resources, Apr 2022]

GATC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017315149).

BP6

Variant 12-120446488-C-T is Benign according to our data. Variant chr12-120446488-C-T is described in ClinVar as [Benign]. Clinvar id is 1294746.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATC	NM_176818.3 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant	1/4	ENST00000551765.6
GATC	NR_033684.2 linkuse as main transcript	n.45C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATC	ENST00000551765.6 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant	1/4	1	NM_176818.3	P1
GATC	ENST00000548171.1 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

6916

AN:

152226

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0944

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0595

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0564

AC:

13974

AN:

247570

Hom.:

569

AF XY:

0.0610

AC XY:

8169

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.00679

Gnomad AMR exome

AF:

0.0281

Gnomad ASJ exome

AF:

0.0561

Gnomad EAS exome

AF:

0.00301

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0983

Gnomad NFE exome

AF:

0.0609

Gnomad OTH exome

AF:

0.0545

GnomAD4 exome

AF:

0.0577

AC:

83976

AN:

1454402

Hom.:

2813

Cov.:

AF XY:

0.0598

AC XY:

43198

AN XY:

722538

show subpopulations

Gnomad4 AFR exome

AF:

0.00840

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0528

Gnomad4 EAS exome

AF:

0.00185

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0931

Gnomad4 NFE exome

AF:

0.0574

Gnomad4 OTH exome

AF:

0.0548

GnomAD4 genome

AF:

0.0453

AC:

6908

AN:

152344

Hom.:

261

Cov.:

AF XY:

0.0473

AC XY:

3525

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.0386

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0996

Gnomad4 FIN

AF:

0.0944

Gnomad4 NFE

AF:

0.0595

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0552

Hom.:

340

Bravo

AF:

0.0373

TwinsUK

AF:

0.0585

AC:

217

ALSPAC

AF:

0.0618

AC:

238

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0571

AC:

491

ExAC

AF:

0.0556

AC:

6751

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

REVEL

Benign

0.076

Sift

Uncertain

0.0070

Sift4G

Benign

0.061

Polyphen

0.0

Vest4

0.20

MPC

0.46

ClinPred

0.067

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.36

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