12-120456882-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176818.3(GATC):c.255-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,142 control chromosomes in the GnomAD database, including 3,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3470 hom., cov: 32)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-120456882-C-T is Benign according to our data. Variant chr12-120456882-C-T is described in ClinVar as [Benign]. Clinvar id is 1263252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATC	NM_176818.3	c.255-194C>T		intron_variant		ENST00000551765.6
GATC	NR_033684.2	n.390-194C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATC	ENST00000551765.6	c.255-194C>T		intron_variant		1	NM_176818.3	P1
GATC	ENST00000229384.5	c.24-194C>T		intron_variant		2
GATC	ENST00000548171.1	c.353-194C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30831 AN: 152024 Hom.: 3471 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30840 AN: 152142 Hom.: 3470 Cov.: 32 AF XY: 0.200 AC XY: 14914 AN XY: 74388

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.203

Alfa AF: 0.190 Hom.: 1447

Bravo AF: 0.209

Asia WGS AF: 0.186 AC: 647 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	5.4
Dann	Benign	0.85

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: rs7137953; hg19: chr12-120894685;