12-120459969-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_176818.3(GATC):c.*10T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,606,764 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (89 hom.)
• Consequence: GATC NM_176818.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 12-120459969-T-G is Benign according to our data. Variant chr12-120459969-T-G is described in ClinVar as [Benign]. Clinvar id is 1236331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATC	NM_176818.3	c.*10T>G		3_prime_UTR_variant	4/4	ENST00000551765.6
GATC	NR_033684.2	n.556T>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATC	ENST00000551765.6	c.*10T>G		3_prime_UTR_variant	4/4	1	NM_176818.3	P1
GATC	ENST00000548171.1	c.*153T>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2
GATC	ENST00000229384.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3455 AN: 152214 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.00552 AC: 1383 AN: 250608 Hom.: 47 AF XY: 0.00388 AC XY: 526 AN XY: 135464

Gnomad AFR exome AF: 0.0756

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000985

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00214 AC: 3114 AN: 1454432 Hom.: 89 Cov.: 27 AF XY: 0.00185 AC XY: 1340 AN XY: 723944

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.00361

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.00454

GnomAD4 genome AF: 0.0227 AC: 3453 AN: 152332 Hom.: 133 Cov.: 32 AF XY: 0.0214 AC XY: 1597 AN XY: 74500

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0175 Hom.: 21

Bravo AF: 0.0260

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	6.8
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs115350072; hg19: chr12-120897772;