rs17360461

chr4-151744372-G-A

Variant summary

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

The NM_004564.3(GATB):c.327+14400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,216 control chromosomes in the GnomAD database, including 273 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 0.050 (273 hom., cov: 33)
• Consequence: GATB NM_004564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.327+14400C>T		intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.327+14400C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.327+14400C>T		intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7644 AN: 152098 Hom.: 273 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.0440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0502 AC: 7646 AN: 152216 Hom.: 273 Cov.: 33 AF XY: 0.0457 AC XY: 3400 AN XY: 74428

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0829

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0614 Hom.: 61

Bravo AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.42

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: rs17360461; hg19: chr4-152665524; COSMIC: COSV56132763;