chr12-120457486-C-G

Variant names:

• chr12-120457486-C-G
• rs3847971
• NM_176818.3:c.358+307C>G

Variant summary

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

The NM_176818.3(GATC):​c.358+307C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,900 control chromosomes in the GnomAD database, including 41,679 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 0.73 (41679 hom., cov: 30)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATC	NM_176818.3	c.358+307C>G		intron_variant	Intron 3 of 3	ENST00000551765.6	NP_789788.1
GATC	NR_033684.2	n.493+307C>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATC	ENST00000551765.6	c.358+307C>G		intron_variant	Intron 3 of 3	1	NM_176818.3	ENSP00000446872.1
ENSG00000111780	ENST00000551806.1	c.451+307C>G		intron_variant	Intron 4 of 4	3		ENSP00000450281.1
GATC	ENST00000229384.5	c.127+307C>G		intron_variant	Intron 2 of 2	2		ENSP00000229384.5
GATC	ENST00000548171.1	n.*90+307C>G		intron_variant	Intron 4 of 4	2		ENSP00000448397.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110821 AN: 151780 Hom.: 41622 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.730 AC: 110937 AN: 151900 Hom.: 41679 Cov.: 30 AF XY: 0.730 AC XY: 54216 AN XY: 74218

African (AFR) AF: 0.914 AC: 37902 AN: 41464

American (AMR) AF: 0.611 AC: 9307 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3757 AN: 5168

South Asian (SAS) AF: 0.679 AC: 3259 AN: 4798

European-Finnish (FIN) AF: 0.689 AC: 7243 AN: 10506

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44825 AN: 67948

Other (OTH) AF: 0.659 AC: 1388 AN: 2106

Alfa AF: 0.589 Hom.: 1586

Bravo AF: 0.729

Asia WGS AF: 0.709 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.81
PhyloP100		-2.3
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: rs3847971; hg19: chr12-120895289;