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GeneBe

4-151688674-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004564.3(GATB):c.1287T>G(p.Thr429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,612,322 control chromosomes in the GnomAD database, including 1,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 66 hom., cov: 31)
Exomes 𝑓: 0.036 ( 1018 hom. )

Consequence

GATB
NM_004564.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.275
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-151688674-A-C is Benign according to our data. Variant chr4-151688674-A-C is described in ClinVar as [Benign]. Clinvar id is 3056173.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.275 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3837/152196) while in subpopulation NFE AF= 0.0407 (2766/68010). AF 95% confidence interval is 0.0394. There are 66 homozygotes in gnomad4. There are 1703 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 65 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GATBNM_004564.3 linkuse as main transcriptc.1287T>G p.Thr429= synonymous_variant 10/13 ENST00000263985.11
GATBNM_001363341.2 linkuse as main transcriptc.1287T>G p.Thr429= synonymous_variant 10/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GATBENST00000263985.11 linkuse as main transcriptc.1287T>G p.Thr429= synonymous_variant 10/131 NM_004564.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0252
AC:
3834
AN:
152078
Hom.:
65
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00693
Gnomad AMI
AF:
0.0658
Gnomad AMR
AF:
0.0166
Gnomad ASJ
AF:
0.0234
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00665
Gnomad FIN
AF:
0.0283
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0406
Gnomad OTH
AF:
0.0234
GnomAD3 exomes
AF:
0.0263
AC:
6568
AN:
249644
Hom.:
111
AF XY:
0.0266
AC XY:
3586
AN XY:
134844
show subpopulations
Gnomad AFR exome
AF:
0.00573
Gnomad AMR exome
AF:
0.0116
Gnomad ASJ exome
AF:
0.0181
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00793
Gnomad FIN exome
AF:
0.0324
Gnomad NFE exome
AF:
0.0423
Gnomad OTH exome
AF:
0.0272
GnomAD4 exome
AF:
0.0357
AC:
52153
AN:
1460126
Hom.:
1018
Cov.:
32
AF XY:
0.0350
AC XY:
25448
AN XY:
726230
show subpopulations
Gnomad4 AFR exome
AF:
0.00629
Gnomad4 AMR exome
AF:
0.0129
Gnomad4 ASJ exome
AF:
0.0185
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00854
Gnomad4 FIN exome
AF:
0.0348
Gnomad4 NFE exome
AF:
0.0418
Gnomad4 OTH exome
AF:
0.0284
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0252
AC:
3837
AN:
152196
Hom.:
66
Cov.:
31
AF XY:
0.0229
AC XY:
1703
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00691
Gnomad4 AMR
AF:
0.0166
Gnomad4 ASJ
AF:
0.0234
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00686
Gnomad4 FIN
AF:
0.0283
Gnomad4 NFE
AF:
0.0407
Gnomad4 OTH
AF:
0.0232
Alfa
AF:
0.0351
Hom.:
66
Bravo
AF:
0.0235
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.0368
EpiControl
AF:
0.0378

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

GATB-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 25, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
5.5
Dann
Benign
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62327344; hg19: chr4-152609826; COSMIC: COSV56130343; COSMIC: COSV56130343; API