rs710187

Variant names:

• chr22-37808082-C-A
• rs710187
• NM_014291.4:c.115C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• 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
• Publications: 41 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	NM_014291.4	MANE Select	c.115C>A	p.Arg39Ser	missense	Exon 1 of 9	NP_055106.1
	GCAT	NM_001171690.2		c.115C>A	p.Arg39Ser	missense	Exon 1 of 10	NP_001165161.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	ENST00000248924.11	TSL:1 MANE Select	c.115C>A	p.Arg39Ser	missense	Exon 1 of 9	ENSP00000248924.6
	GCAT	ENST00000323205.10	TSL:2	c.115C>A	p.Arg39Ser	missense	Exon 1 of 10	ENSP00000371110.3
	GCAT	ENST00000451984.1	TSL:3	c.67C>A	p.Arg23Ser	missense	Exon 1 of 4	ENSP00000388151.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31314

American (AMR) AF: 0.00 AC: 0 AN: 38796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25354

East Asian (EAS) AF: 0.00 AC: 0 AN: 35828

South Asian (SAS) AF: 0.00 AC: 0 AN: 80900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092032

Other (OTH) AF: 0.00 AC: 0 AN: 58672

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.74	P
Vest4		0.66
MutPred		0.39		Gain of glycosylation at R39 (P = 0.0073)
MVP		0.99
MPC		0.33
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.78
gMVP		0.48
Mutation Taster		=46/54	disease causing

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: rs710187; hg19: chr22-38204089;