12-120446488-C-T

Position:

• chr12-120446488-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176818.3(GATC):​c.8C>T​(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,606,746 control chromosomes in the GnomAD database, including 3,074 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.045 (261 hom., cov: 33)
  • Exomes 𝑓: 0.058 (2813 hom.)
• Consequence: GATC NM_176818.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.479

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]

ENSG00000111780 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017315149).
• BP6: Variant 12-120446488-C-T is Benign according to our data. Variant chr12-120446488-C-T is described in ClinVar as [Benign]. Clinvar id is 1294746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATC	NM_176818.3	c.8C>T	p.Ser3Leu	missense_variant	1/4	ENST00000551765.6	NP_789788.1
GATC	NR_033684.2	n.45C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATC	ENST00000551765.6	c.8C>T	p.Ser3Leu	missense_variant	1/4	1	NM_176818.3	ENSP00000446872.1
ENSG00000111780	ENST00000551806.1	c.175-169C>T		intron_variant		3		ENSP00000450281.1
GATC	ENST00000548171.1	n.8C>T		non_coding_transcript_exon_variant	1/5	2		ENSP00000448397.1

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6916 AN: 152226 Hom.: 263 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0449

GnomAD3 exomes AF: 0.0564 AC: 13974 AN: 247570 Hom.: 569 AF XY: 0.0610 AC XY: 8169 AN XY: 133896

Gnomad AFR exome AF: 0.00679

Gnomad AMR exome AF: 0.0281

Gnomad ASJ exome AF: 0.0561

Gnomad EAS exome AF: 0.00301

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.0983

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0545

GnomAD4 exome AF: 0.0577 AC: 83976 AN: 1454402 Hom.: 2813 Cov.: 31 AF XY: 0.0598 AC XY: 43198 AN XY: 722538

Gnomad4 AFR exome AF: 0.00840

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.00185

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0931

Gnomad4 NFE exome AF: 0.0574

Gnomad4 OTH exome AF: 0.0548

GnomAD4 genome AF: 0.0453 AC: 6908 AN: 152344 Hom.: 261 Cov.: 33 AF XY: 0.0473 AC XY: 3525 AN XY: 74494

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0552 Hom.: 340

Bravo AF: 0.0373

TwinsUK AF: 0.0585 AC: 217

ALSPAC AF: 0.0618 AC: 238

ESP6500AA AF: 0.00953 AC: 42

ESP6500EA AF: 0.0571 AC: 491

ExAC AF: 0.0556 AC: 6751

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.076
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.061	T
Polyphen		0.0	B
Vest4		0.20
MPC		0.46
ClinPred		0.067	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.36

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: rs17431446; hg19: chr12-120884291; COSMIC: COSV56663466; COSMIC: COSV56663466;