4-151688768-TAA-T

Position:

• chr4-151688768-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004564.3(GATB):​c.1198-7_1198-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,325,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: GATB NM_004564.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.847

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 -10 ACMG points.

• BP6: Variant 4-151688768-TAA-T is Benign according to our data. Variant chr4-151688768-TAA-T is described in ClinVar as [Benign]. Clinvar id is 3056163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1198-7_1198-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1198-7_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.1198-7_1198-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.000661 AC: 97 AN: 146766 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000407

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000595

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00407

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000391

Gnomad OTH AF: 0.000499

GnomAD4 exome AF: 0.0429 AC: 50619 AN: 1179084 Hom.: 0 AF XY: 0.0451 AC XY: 26384 AN XY: 585490

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0395

Gnomad4 ASJ exome AF: 0.0531

Gnomad4 EAS exome AF: 0.0452

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0361

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.000661 AC: 97 AN: 146846 Hom.: 0 Cov.: 0 AF XY: 0.000729 AC XY: 52 AN XY: 71332

Gnomad4 AFR AF: 0.000549

Gnomad4 AMR AF: 0.000407

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.000597

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00407

Gnomad4 NFE AF: 0.000391

Gnomad4 OTH AF: 0.000494

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GATB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 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)		0.020		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;