rs2235222

Variant names:

• chr12-120454390-G-C
• rs2235222
• NM_176818.3:c.255-2686G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176818.3(GATC):​c.255-2686G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,064 control chromosomes in the GnomAD database, including 3,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3541 hom., cov: 32)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 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.255-2686G>C		intron	N/A	NP_789788.1
	GATC	NR_033684.2		n.292-543G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.255-2686G>C		intron	N/A	ENSP00000446872.1
	ENSG00000111780	ENST00000551806.1	TSL:3	c.348-2686G>C		intron	N/A	ENSP00000450281.1
	GATC	ENST00000229384.5	TSL:2	c.24-2686G>C		intron	N/A	ENSP00000229384.5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31043 AN: 151944 Hom.: 3542 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.204 AC: 31053 AN: 152064 Hom.: 3541 Cov.: 32 AF XY: 0.202 AC XY: 15020 AN XY: 74346

African (AFR) AF: 0.295 AC: 12221 AN: 41442

American (AMR) AF: 0.149 AC: 2281 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1293 AN: 3472

East Asian (EAS) AF: 0.157 AC: 811 AN: 5172

South Asian (SAS) AF: 0.203 AC: 976 AN: 4814

European-Finnish (FIN) AF: 0.128 AC: 1353 AN: 10584

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

European-Non Finnish (NFE) AF: 0.167 AC: 11364 AN: 67986

Other (OTH) AF: 0.201 AC: 425 AN: 2110

Alfa AF: 0.186 Hom.: 355

Bravo AF: 0.211

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.45
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: rs2235222; hg19: chr12-120892193;