Variant chr4-151688674-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_004564.3(GATB):c.1287T>G(p.Thr429Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,612,322 control chromosomes in the GnomAD database, including 1,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 66 hom., cov: 31)

Exomes 𝑓: 0.036 ( 1018 hom. )

Consequence

GATB
NM_004564.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.275

Variant links:

Genes affected

GATB (HGNC:8849): (glutamyl-tRNA amidotransferase subunit B) 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 41. [provided by Alliance of Genome Resources, Apr 2022]

GATB links:

GATB (HGNC:):

GATB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-151688674-A-C is Benign according to our data. Variant chr4-151688674-A-C is described in ClinVar as [Benign]. Clinvar id is 3056173.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.275 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3837/152196) while in subpopulation NFE AF= 0.0407 (2766/68010). AF 95% confidence interval is 0.0394. There are 66 homozygotes in gnomad4. There are 1703 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 66 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATB	NM_004564.3 linkuse as main transcript	c.1287T>G	p.Thr429Thr	synonymous_variant	10/13	ENST00000263985.11	NP_004555.1	O75879
GATB	NM_001363341.2 linkuse as main transcript	c.1287T>G	p.Thr429Thr	synonymous_variant	10/12		NP_001350270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATB	ENST00000263985.11 linkuse as main transcript	c.1287T>G	p.Thr429Thr	synonymous_variant	10/13	1	NM_004564.3	ENSP00000263985.6		O75879

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3834

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00693

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00665

Gnomad FIN

AF:

0.0283

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0406

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0263

AC:

6568

AN:

249644

Hom.:

111

AF XY:

0.0266

AC XY:

3586

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.00573

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00793

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0423

Gnomad OTH exome

AF:

0.0272

GnomAD4 exome

AF:

0.0357

AC:

52153

AN:

1460126

Hom.:

1018

Cov.:

AF XY:

0.0350

AC XY:

25448

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.00629

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0185

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00854

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0284

GnomAD4 genome

AF:

0.0252

AC:

3837

AN:

152196

Hom.:

Cov.:

AF XY:

0.0229

AC XY:

1703

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00691

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00686

Gnomad4 FIN

AF:

0.0283

Gnomad4 NFE

AF:

0.0407

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0351

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0368

EpiControl

AF:

0.0378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GATB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 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

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

DANN

Benign

0.63

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