NM_004564.3:c.327+14400C>T

Variant names:

• chr4-151744372-G-A
• rs17360461
• NM_004564.3:c.327+14400C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004564.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATB	NM_004564.3	MANE Select	c.327+14400C>T		intron	N/A	NP_004555.1
	GATB	NM_001363341.2		c.327+14400C>T		intron	N/A	NP_001350270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATB	ENST00000263985.11	TSL:1 MANE Select	c.327+14400C>T		intron	N/A	ENSP00000263985.6
	GATB	ENST00000512306.5	TSL:1	c.327+14400C>T		intron	N/A	ENSP00000420831.1
	GATB	ENST00000515812.5	TSL:5	c.327+14400C>T		intron	N/A	ENSP00000426859.1

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

African (AFR) AF: 0.0147 AC: 612 AN: 41536

American (AMR) AF: 0.0372 AC: 568 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4820

European-Finnish (FIN) AF: 0.0395 AC: 418 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0829 AC: 5637 AN: 68014

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0614 Hom.: 61

Bravo AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.42
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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