4-151688768-T-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_004564.3(GATB):c.1198-6_1198-5insT 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0061 (0 hom.)
• Consequence: GATB NM_004564.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -8 ACMG points.

• BP6: Variant 4-151688768-T-TA is Benign according to our data. Variant chr4-151688768-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 2578970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1198-6_1198-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1198-6_1198-5insT		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.1198-6_1198-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 34 AN: 147034 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000212

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000180

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00609 AC: 7698 AN: 1264076 Hom.: 0 Cov.: 0 AF XY: 0.00592 AC XY: 3721 AN XY: 628842

Gnomad4 AFR exome AF: 0.000834

Gnomad4 AMR exome AF: 0.00900

Gnomad4 ASJ exome AF: 0.00558

Gnomad4 EAS exome AF: 0.00644

Gnomad4 SAS exome AF: 0.00487

Gnomad4 FIN exome AF: 0.00499

Gnomad4 NFE exome AF: 0.00631

Gnomad4 OTH exome AF: 0.00577

GnomAD4 genome AF: 0.000231 AC: 34 AN: 147116 Hom.: 0 Cov.: 0 AF XY: 0.000168 AC XY: 12 AN XY: 71496

Gnomad4 AFR AF: 0.000374

Gnomad4 AMR AF: 0.000203

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000212

Gnomad4 NFE AF: 0.000180

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

GATB: BP4 -

GATB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 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)		0.0		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

Other links and lift over

dbSNP: rs11292952; hg19: chr4-152609920;