NM_176818.3:c.358+307C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176818.3(GATC):​c.358+307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATC	NM_176818.3	c.358+307C>T		intron_variant	Intron 3 of 3	ENST00000551765.6	NP_789788.1
GATC	NR_033684.2	n.493+307C>T		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>T		intron_variant	Intron 3 of 3	1	NM_176818.3	ENSP00000446872.1
ENSG00000111780	ENST00000551806.1	c.451+307C>T		intron_variant	Intron 4 of 4	3		ENSP00000450281.1
GATC	ENST00000229384.5	c.127+307C>T		intron_variant	Intron 2 of 2	2		ENSP00000229384.5
GATC	ENST00000548171.1	n.*90+307C>T		intron_variant	Intron 4 of 4	2		ENSP00000448397.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.93
PhyloP100		-2.3

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;