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12-120446525-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_176818.3(GATC):c.45C>T(p.Gly15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,601,406 control chromosomes in the GnomAD database, including 81,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5893 hom., cov: 33)
Exomes 𝑓: 0.32 ( 75379 hom. )

Consequence

GATC
NM_176818.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.353
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 -13 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=-0.21).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-120446525-C-T is Benign according to our data. Variant chr12-120446525-C-T is described in ClinVar as [Benign]. Clinvar id is 1246559.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=-0.353 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GATCNM_176818.3 linkuse as main transcriptc.45C>T p.Gly15= synonymous_variant 1/4 ENST00000551765.6
GATCNR_033684.2 linkuse as main transcriptn.82C>T non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GATCENST00000551765.6 linkuse as main transcriptc.45C>T p.Gly15= synonymous_variant 1/41 NM_176818.3 P1
GATCENST00000548171.1 linkuse as main transcriptc.45C>T p.Gly15= synonymous_variant, NMD_transcript_variant 1/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.258
AC:
39125
AN:
151870
Hom.:
5881
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.109
Gnomad AMI
AF:
0.245
Gnomad AMR
AF:
0.272
Gnomad ASJ
AF:
0.227
Gnomad EAS
AF:
0.495
Gnomad SAS
AF:
0.283
Gnomad FIN
AF:
0.331
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.317
Gnomad OTH
AF:
0.247
GnomAD3 exomes
AF:
0.300
AC:
73308
AN:
244514
Hom.:
11924
AF XY:
0.301
AC XY:
39968
AN XY:
132564
show subpopulations
Gnomad AFR exome
AF:
0.102
Gnomad AMR exome
AF:
0.295
Gnomad ASJ exome
AF:
0.224
Gnomad EAS exome
AF:
0.492
Gnomad SAS exome
AF:
0.286
Gnomad FIN exome
AF:
0.320
Gnomad NFE exome
AF:
0.306
Gnomad OTH exome
AF:
0.290
GnomAD4 exome
AF:
0.318
AC:
460573
AN:
1449418
Hom.:
75379
Cov.:
39
AF XY:
0.317
AC XY:
228330
AN XY:
719778
show subpopulations
Gnomad4 AFR exome
AF:
0.0998
Gnomad4 AMR exome
AF:
0.292
Gnomad4 ASJ exome
AF:
0.229
Gnomad4 EAS exome
AF:
0.497
Gnomad4 SAS exome
AF:
0.289
Gnomad4 FIN exome
AF:
0.316
Gnomad4 NFE exome
AF:
0.324
Gnomad4 OTH exome
AF:
0.306
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.258
AC:
39149
AN:
151988
Hom.:
5893
Cov.:
33
AF XY:
0.261
AC XY:
19372
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.108
Gnomad4 AMR
AF:
0.273
Gnomad4 ASJ
AF:
0.227
Gnomad4 EAS
AF:
0.495
Gnomad4 SAS
AF:
0.284
Gnomad4 FIN
AF:
0.331
Gnomad4 NFE
AF:
0.317
Gnomad4 OTH
AF:
0.244
Alfa
AF:
0.295
Hom.:
7388
Bravo
AF:
0.248
Asia WGS
AF:
0.346
AC:
1206
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
Cadd
Benign
8.5
Dann
Benign
0.84
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs2235217; hg19: chr12-120884328; COSMIC: COSV56663308; COSMIC: COSV56663308; API