22-37808082-C-G

Position:

• chr22-37808082-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014291.4(GCAT):​c.115C>G​(p.Arg39Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GCAT NM_014291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.86

Genes affected

GCAT (HGNC:4188): (glycine C-acetyltransferase) The degradation of L-threonine to glycine consists of a two-step biochemical pathway involving the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is first converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. This gene encodes the second enzyme in this pathway, which then catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The encoded enzyme is considered a class II pyridoxal-phosphate-dependent aminotransferase. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 14. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCAT	NM_014291.4	c.115C>G	p.Arg39Gly	missense_variant	1/9	ENST00000248924.11	NP_055106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCAT	ENST00000248924.11	c.115C>G	p.Arg39Gly	missense_variant	1/9	1	NM_014291.4	ENSP00000248924	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1418416 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 702296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	.;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Pathogenic	3.1	M;M;.
MutationTaster	Benign	4.6e-10	P;P
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.1	D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.85	.;P;.
Vest4		0.58
MutPred		0.42		Loss of MoRF binding (P = 0.0176);Loss of MoRF binding (P = 0.0176);Loss of MoRF binding (P = 0.0176);
MVP		0.99
MPC		0.45
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.87
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs710187; hg19: chr22-38204089;