12-120446650-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_176818.3(GATC):​c.82-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,607,166 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

GATC
NM_176818.3 splice_region, intron

Scores

2
Splicing: ADA: 0.00003967
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.372
Variant links:
Genes affected
GATC (HGNC:25068): (glutamyl-tRNA amidotransferase subunit C) 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 42. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATCNM_176818.3 linkc.82-7C>T splice_region_variant, intron_variant Intron 1 of 3 ENST00000551765.6 NP_789788.1 O43716
GATCNR_033684.2 linkn.119-7C>T splice_region_variant, intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATCENST00000551765.6 linkc.82-7C>T splice_region_variant, intron_variant Intron 1 of 3 1 NM_176818.3 ENSP00000446872.1 O43716
ENSG00000111780ENST00000551806.1 linkc.175-7C>T splice_region_variant, intron_variant Intron 2 of 4 3 ENSP00000450281.1 H0YIV9
GATCENST00000229384 linkc.-157C>T 5_prime_UTR_variant Exon 1 of 3 2 ENSP00000229384.5 J3KMY1
GATCENST00000548171.1 linkn.82-7C>T splice_region_variant, intron_variant Intron 1 of 4 2 ENSP00000448397.1 F8VRU3

Frequencies

GnomAD3 genomes
AF:
0.000788
AC:
120
AN:
152252
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000313
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00151
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000663
AC:
163
AN:
245814
Hom.:
0
AF XY:
0.000607
AC XY:
81
AN XY:
133364
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.0000879
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000987
Gnomad NFE exome
AF:
0.00138
Gnomad OTH exome
AF:
0.000333
GnomAD4 exome
AF:
0.00136
AC:
1981
AN:
1454796
Hom.:
2
Cov.:
33
AF XY:
0.00134
AC XY:
967
AN XY:
722882
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.000113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.000116
Gnomad4 NFE exome
AF:
0.00169
Gnomad4 OTH exome
AF:
0.00155
GnomAD4 genome
AF:
0.000794
AC:
121
AN:
152370
Hom.:
0
Cov.:
33
AF XY:
0.000698
AC XY:
52
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00153
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00114
Hom.:
0
Bravo
AF:
0.000703
EpiCase
AF:
0.00104
EpiControl
AF:
0.00130

ClinVar

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

Submissions by phenotype

Combined oxidative phosphorylation deficiency 42 Uncertain:1
Sep 15, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
7.3
DANN
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000040
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.10
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: rs188545590; hg19: chr12-120884453; API