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GeneBe

4-151688632-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004564.3(GATB):c.1329G>A(p.Glu443=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,603,940 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 77 hom., cov: 32)
Exomes 𝑓: 0.0037 ( 258 hom. )

Consequence

GATB
NM_004564.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.003862
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60
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 -19 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=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-151688632-C-T is Benign according to our data. Variant chr4-151688632-C-T is described in ClinVar as [Benign]. Clinvar id is 1287980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=1.6 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GATBNM_004564.3 linkuse as main transcriptc.1329G>A p.Glu443= splice_region_variant, synonymous_variant 10/13 ENST00000263985.11
GATBNM_001363341.2 linkuse as main transcriptc.1329G>A p.Glu443= splice_region_variant, synonymous_variant 10/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GATBENST00000263985.11 linkuse as main transcriptc.1329G>A p.Glu443= splice_region_variant, synonymous_variant 10/131 NM_004564.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00905
AC:
1377
AN:
152162
Hom.:
76
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00222
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0747
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0207
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.0147
AC:
3550
AN:
240772
Hom.:
186
AF XY:
0.0113
AC XY:
1463
AN XY:
129876
show subpopulations
Gnomad AFR exome
AF:
0.00193
Gnomad AMR exome
AF:
0.0962
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0194
Gnomad SAS exome
AF:
0.000439
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000252
Gnomad OTH exome
AF:
0.0138
GnomAD4 exome
AF:
0.00374
AC:
5423
AN:
1451660
Hom.:
258
Cov.:
32
AF XY:
0.00324
AC XY:
2340
AN XY:
721692
show subpopulations
Gnomad4 AFR exome
AF:
0.00116
Gnomad4 AMR exome
AF:
0.0920
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0296
Gnomad4 SAS exome
AF:
0.000372
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000118
Gnomad4 OTH exome
AF:
0.00342
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00910
AC:
1386
AN:
152280
Hom.:
77
Cov.:
32
AF XY:
0.0113
AC XY:
839
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00221
Gnomad4 AMR
AF:
0.0751
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0207
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00189
Hom.:
7
Bravo
AF:
0.0123
Asia WGS
AF:
0.0130
AC:
45
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
GATB-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 05, 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
-0.32
Cadd
Benign
12
Dann
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0039
dbscSNV1_RF
Benign
0.022
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: rs75029272; hg19: chr4-152609784; COSMIC: COSV56134418; COSMIC: COSV56134418; API