4-151671317-A-ATTAC

Variant summary

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

The NM_004564.3(GATB):c.1546-16_1546-15insGTAA variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,603,230 control chromosomes in the GnomAD database, including 215,521 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (29058 hom., cov: 0)
  • Exomes 𝑓: 0.50 (186463 hom.)
• Consequence: GATB NM_004564.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 4-151671317-A-ATTAC is Benign according to our data. Variant chr4-151671317-A-ATTAC is described in ClinVar as [Benign]. Clinvar id is 1256843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1546-16_1546-15insGTAA		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1411-16_1411-15insGTAA		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.1546-16_1546-15insGTAA		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89762 AN: 151408 Hom.: 29005 Cov.: 0

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.579

GnomAD3 exomes AF: 0.510 AC: 127567 AN: 249926 Hom.: 34170 AF XY: 0.513 AC XY: 69327 AN XY: 135270

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.503

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.499 AC: 724708 AN: 1451704 Hom.: 186463 Cov.: 31 AF XY: 0.503 AC XY: 363194 AN XY: 722674

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.593 AC: 89870 AN: 151526 Hom.: 29058 Cov.: 0 AF XY: 0.588 AC XY: 43542 AN XY: 74002

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.581

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34076826; hg19: chr4-152592469;