4-151671039-T-C

Position:

• chr4-151671039-T-C

Variant summary

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

The NM_004564.3(GATB):​c.*135A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,021,494 control chromosomes in the GnomAD database, including 146,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29569 hom., cov: 32)
  • Exomes 𝑓: 0.51 (116460 hom.)
• Consequence: GATB NM_004564.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07

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]

GATB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 4-151671039-T-C is Benign according to our data. Variant chr4-151671039-T-C is described in ClinVar as [Benign]. Clinvar id is 1261015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATB	NM_004564.3	c.*135A>G		3_prime_UTR_variant	13/13	ENST00000263985.11	NP_004555.1
GATB	NM_001363341.2	c.*135A>G		3_prime_UTR_variant	12/12		NP_001350270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATB	ENST00000263985	c.*135A>G		3_prime_UTR_variant	13/13	1	NM_004564.3	ENSP00000263985.6

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90873 AN: 151966 Hom.: 29519 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.511 AC: 444288 AN: 869410 Hom.: 116460 Cov.: 11 AF XY: 0.515 AC XY: 230532 AN XY: 447398

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.494

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.598 AC: 90977 AN: 152084 Hom.: 29569 Cov.: 32 AF XY: 0.594 AC XY: 44121 AN XY: 74330

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.583

Alfa AF: 0.514 Hom.: 20079

Bravo AF: 0.606

Asia WGS AF: 0.566 AC: 1969 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	0.31
DANN	Benign	0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4571; hg19: chr4-152592191;