4-151688548-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004564.3(GATB):c.1331+82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,419,184 control chromosomes in the GnomAD database, including 188,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (25311 hom., cov: 31)
  • Exomes 𝑓: 0.50 (162791 hom.)
• Consequence: GATB NM_004564.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-151688548-A-C is Benign according to our data. Variant chr4-151688548-A-C is described in ClinVar as [Benign]. Clinvar id is 1248000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1331+82T>G		intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1331+82T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.1331+82T>G		intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84924 AN: 151312 Hom.: 25279 Cov.: 31

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.501 AC: 635578 AN: 1267754 Hom.: 162791 AF XY: 0.504 AC XY: 316253 AN XY: 627278

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.561 AC: 85004 AN: 151430 Hom.: 25311 Cov.: 31 AF XY: 0.557 AC XY: 41222 AN XY: 74018

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.561

Alfa AF: 0.539 Hom.: 2875

Bravo AF: 0.565

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.57
Dann	Benign	0.40

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: rs6535815; hg19: chr4-152609700; COSMIC: COSV56132394; COSMIC: COSV56132394;