12-120456882-C-T

Variant names:

• chr12-120456882-C-T
• rs7137953
• NM_176818.3:c.255-194C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

GATC Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 42

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000111780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	NM_176818.3	MANE Select	c.255-194C>T		intron	N/A	NP_789788.1
	GATC	NR_033684.2		n.390-194C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.255-194C>T		intron	N/A	ENSP00000446872.1
	ENSG00000111780	ENST00000551806.1	TSL:3	c.348-194C>T		intron	N/A	ENSP00000450281.1
	GATC	ENST00000229384.5	TSL:2	c.24-194C>T		intron	N/A	ENSP00000229384.5

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

African (AFR) AF: 0.281 AC: 11647 AN: 41474

American (AMR) AF: 0.154 AC: 2348 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3472

East Asian (EAS) AF: 0.157 AC: 813 AN: 5194

South Asian (SAS) AF: 0.204 AC: 984 AN: 4816

European-Finnish (FIN) AF: 0.128 AC: 1361 AN: 10604

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11640 AN: 67982

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.186 Hom.: 1876

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

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.4
DANN	Benign	0.85
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7137953; hg19: chr12-120894685;