4-151679994-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004564.3(GATB):c.1332-103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 977,720 control chromosomes in the GnomAD database, including 131,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (25403 hom., cov: 32)
  • Exomes 𝑓: 0.50 (106386 hom.)
• Consequence: GATB NM_004564.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-151679994-T-G is Benign according to our data. Variant chr4-151679994-T-G is described in ClinVar as [Benign]. Clinvar id is 1183896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATB	NM_004564.3	c.1332-103A>C		intron_variant		ENST00000263985.11
GATB	NM_001363341.2	c.1332-103A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATB	ENST00000263985.11	c.1332-103A>C		intron_variant		1	NM_004564.3	P1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85453 AN: 151898 Hom.: 25371 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.504 AC: 416394 AN: 825702 Hom.: 106386 AF XY: 0.510 AC XY: 220042 AN XY: 431752

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.563 AC: 85542 AN: 152018 Hom.: 25403 Cov.: 32 AF XY: 0.560 AC XY: 41592 AN XY: 74328

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.556

Alfa AF: 0.539 Hom.: 2857

Bravo AF: 0.566

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.5
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs907237; hg19: chr4-152601146; COSMIC: COSV56131277; COSMIC: COSV56131277;