chr12-120459849-T-C

Position:

• chr12-120459849-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176818.3(GATC):​c.359-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,384,158 control chromosomes in the GnomAD database, including 322,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41803 hom., cov: 32)
  • Exomes 𝑓: 0.67 (280663 hom.)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.37

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]

ENSG00000111780 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 12-120459849-T-C is Benign according to our data. Variant chr12-120459849-T-C is described in ClinVar as [Benign]. Clinvar id is 1239885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATC	NM_176818.3	c.359-58T>C		intron_variant		ENST00000551765.6	NP_789788.1
GATC	NR_033684.2	n.494-58T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATC	ENST00000551765.6	c.359-58T>C		intron_variant		1	NM_176818.3	ENSP00000446872.1
ENSG00000111780	ENST00000551806.1	c.452-58T>C		intron_variant		3		ENSP00000450281.1
GATC	ENST00000229384.5	c.128-58T>C		intron_variant		2		ENSP00000229384.5
GATC	ENST00000548171.1	n.*91-58T>C		intron_variant		2		ENSP00000448397.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111041 AN: 152008 Hom.: 41741 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.667

GnomAD4 exome AF: 0.673 AC: 828718 AN: 1232032 Hom.: 280663 AF XY: 0.673 AC XY: 418358 AN XY: 622024

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.705

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.680

GnomAD4 genome AF: 0.731 AC: 111161 AN: 152126 Hom.: 41803 Cov.: 32 AF XY: 0.731 AC XY: 54324 AN XY: 74354

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.661

Alfa AF: 0.701 Hom.: 4459

Bravo AF: 0.730

Asia WGS AF: 0.708 AC: 2466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.51

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: rs28390349; hg19: chr12-120897652;