Genetic Variant GATB:c.1411-1325T>C (chr4-151674221-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004564.3(GATB):c.1411-1325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,042 control chromosomes in the GnomAD database, including 29,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 29330 hom., cov: 31)

Exomes 𝑓: 0.46 ( 6 hom. )

Consequence

GATB
NM_004564.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.188

Publications

8 publications found

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]

GATB links:

LOC107986197 (HGNC:):

LOC107986197 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004564.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATB	NM_004564.3	MANE Select	c.1411-1325T>C		intron	N/A	NP_004555.1	O75879
	GATB	NM_001363341.2		c.1411-2919T>C		intron	N/A	NP_001350270.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATB	ENST00000263985.11	TSL:1 MANE Select	c.1411-1325T>C	intron	N/A	ENSP00000263985.6	O75879
GATB	ENST00000922191.1		c.1408-1325T>C	intron	N/A	ENSP00000592250.1
GATB	ENST00000871436.1		c.1333-1325T>C	intron	N/A	ENSP00000541495.1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90511

AN:

151878

Hom.:

29281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.457

AC:

AN:

Hom.:

Cov.:

AF XY:

0.393

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.458

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.596

AC:

90614

AN:

151996

Hom.:

29330

Cov.:

AF XY:

0.592

AC XY:

43946

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.869

AC:

36055

AN:

41470

American (AMR)

AF:

0.485

AC:

7413

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1679

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2513

AN:

5142

South Asian (SAS)

AF:

0.615

AC:

2959

AN:

4814

European-Finnish (FIN)

AF:

0.471

AC:

4962

AN:

10546

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33274

AN:

67954

Other (OTH)

AF:

0.582

AC:

1231

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1690

3379

5069

6758

8448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.507

Hom.:

7452

Bravo

AF:

0.603

Asia WGS

AF:

0.566

AC:

1970

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.2

(source)

DANN

Benign

0.41

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over