Variant 4-151688632-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004564.3(GATB):c.1329G>A(p.Glu443Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,603,940 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 77 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 258 hom. )

Consequence

GATB
NM_004564.3 splice_region, synonymous

Scores

Splicing: ADA: 0.003862

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.60

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-151688632-C-T is Benign according to our data. Variant chr4-151688632-C-T is described in ClinVar as [Benign]. Clinvar id is 1287980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATB	NM_004564.3 linkuse as main transcript	c.1329G>A	p.Glu443Glu	splice_region_variant, synonymous_variant	10/13	ENST00000263985.11	NP_004555.1	O75879
GATB	NM_001363341.2 linkuse as main transcript	c.1329G>A	p.Glu443Glu	splice_region_variant, 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.1329G>A	p.Glu443Glu	splice_region_variant, synonymous_variant	10/13	1	NM_004564.3	ENSP00000263985.6		O75879

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1377

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0747

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0207

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.0147

AC:

3550

AN:

240772

Hom.:

186

AF XY:

0.0113

AC XY:

1463

AN XY:

129876

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.0962

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0194

Gnomad SAS exome

AF:

0.000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000252

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00374

AC:

5423

AN:

1451660

Hom.:

258

Cov.:

AF XY:

0.00324

AC XY:

2340

AN XY:

721692

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.0920

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0296

Gnomad4 SAS exome

AF:

0.000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.00342

GnomAD4 genome

AF:

0.00910

AC:

1386

AN:

152280

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

839

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0207

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

GATB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 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

-0.32

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0039

dbscSNV1_RF

Benign

0.022

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