4-151688768-TA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004564.3(GATB):c.1198-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27698 hom., cov: 0)
  • Exomes 𝑓: 0.49 (29774 hom.)
  • Failed GnomAD Quality Control
• Consequence: GATB NM_004564.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0660

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-151688768-TA-T is Benign according to our data. Variant chr4-151688768-TA-T is described in ClinVar as [Benign]. Clinvar id is 1252303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1198-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1198-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.1198-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 86894 AN: 146786 Hom.: 27659 Cov.: 0

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.582

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.491 AC: 581388 AN: 1184726 Hom.: 29774 Cov.: 0 AF XY: 0.491 AC XY: 289434 AN XY: 589968

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.592 AC: 86970 AN: 146864 Hom.: 27698 Cov.: 0 AF XY: 0.588 AC XY: 41961 AN XY: 71362

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined oxidative phosphorylation deficiency 41 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

GATB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11292952; hg19: chr4-152609920;