4-151674221-A-G

Position:

• chr4-151674221-A-G

Variant summary

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

The NM_004564.3(GATB):​c.1411-1325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,042 control chromosomes in the GnomAD database, including 29,336 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 (29330 hom., cov: 31)
  • Exomes 𝑓: 0.46 (6 hom.)
• Consequence: GATB NM_004564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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]

LOC107986197 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATB	NM_004564.3	c.1411-1325T>C		intron_variant		ENST00000263985.11	NP_004555.1
LOC107986197	XR_001741447.3	n.2633A>G		non_coding_transcript_exon_variant	1/2
GATB	NM_001363341.2	c.1411-2919T>C		intron_variant			NP_001350270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATB	ENST00000263985.11	c.1411-1325T>C		intron_variant		1	NM_004564.3	ENSP00000263985	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90511 AN: 151878 Hom.: 29281 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.457 AC: 21 AN: 46 Hom.: 6 Cov.: 0 AF XY: 0.393 AC XY: 11 AN XY: 28

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.596 AC: 90614 AN: 151996 Hom.: 29330 Cov.: 31 AF XY: 0.592 AC XY: 43946 AN XY: 74284

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.582

Alfa AF: 0.481 Hom.: 4033

Bravo AF: 0.603

Asia WGS AF: 0.566 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.41

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: rs1896883; hg19: chr4-152595373;