4-151688542-A-G

Position:

• chr4-151688542-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000263985.11(GATB):​c.1331+88T>C 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 1,324,886 control chromosomes in the GnomAD database, including 176,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (25287 hom., cov: 31)
  • Exomes 𝑓: 0.50 (151232 hom.)
• Consequence: GATB ENST00000263985.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.512

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 4-151688542-A-G is Benign according to our data. Variant chr4-151688542-A-G is described in ClinVar as [Benign]. Clinvar id is 1179746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATB	NM_004564.3	c.1331+88T>C		intron_variant		ENST00000263985.11	NP_004555.1
GATB	NM_001363341.2	c.1331+88T>C		intron_variant			NP_001350270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATB	ENST00000263985.11	c.1331+88T>C		intron_variant		1	NM_004564.3	ENSP00000263985	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84901 AN: 151378 Hom.: 25256 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.502 AC: 588592 AN: 1173390 Hom.: 151232 AF XY: 0.504 AC XY: 294998 AN XY: 584934

Gnomad4 AFR exome AF: 0.787

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.561 AC: 84980 AN: 151496 Hom.: 25287 Cov.: 31 AF XY: 0.556 AC XY: 41205 AN XY: 74044

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.558

Alfa AF: 0.539 Hom.: 2873

Bravo AF: 0.565

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.39

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: rs6535814; hg19: chr4-152609694; COSMIC: COSV56132382; COSMIC: COSV56132382;