4-151675388-T-C

Position:

• chr4-151675388-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004564.3(GATB):​c.1411-2492A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,476 control chromosomes in the GnomAD database, including 30,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (30074 hom., cov: 32)
  • Exomes 𝑓: 0.58 (76 hom.)
• Consequence: GATB NM_004564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1411-2492A>G		intron_variant		ENST00000263985.11
LOC107986197	XR_001741447.3	n.3800T>C		non_coding_transcript_exon_variant	1/2
GATB	NM_001363341.2	c.1411-4086A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.1411-2492A>G		intron_variant		1	NM_004564.3	P1
	ENST00000514269.1	n.906T>C		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91388 AN: 151938 Hom.: 30024 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.581 AC: 244 AN: 420 Hom.: 76 Cov.: 0 AF XY: 0.570 AC XY: 180 AN XY: 316

Gnomad4 AFR exome AF: 0.917

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.602 AC: 91492 AN: 152056 Hom.: 30074 Cov.: 32 AF XY: 0.597 AC XY: 44375 AN XY: 74312

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.586

Alfa AF: 0.565 Hom.: 3215

Bravo AF: 0.609

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.69

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: rs3749562; hg19: chr4-152596540;