rs710187

Positions:

• chr22-37808082-C-A
• chr22-37808082-C-G
• chr22-37808082-C-T

Variant summary

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

The NM_014291.4(GCAT):​c.115C>A​(p.Arg39Ser) 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, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCAT	NM_014291.4	c.115C>A	p.Arg39Ser	missense_variant	1/9	ENST00000248924.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCAT	ENST00000248924.11	c.115C>A	p.Arg39Ser	missense_variant	1/9	1	NM_014291.4	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.6	M;M;.
MutationTaster	Benign	4.3e-10	P;P
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.020	D;D;D
Sift4G	Uncertain	0.017	D;T;D
Polyphen		0.74	.;P;.
Vest4		0.66
MutPred		0.39		Gain of glycosylation at R39 (P = 0.0073);Gain of glycosylation at R39 (P = 0.0073);Gain of glycosylation at R39 (P = 0.0073);
MVP		0.99
MPC		0.33
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.78
gMVP		0.48

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: rs710187; hg19: chr22-38204089;