22-37808082-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014291.4(GCAT):​c.115C>T​(p.Arg39Cys) variant causes a missense change. The variant allele was found at a frequency of 0.56 in 1,569,746 control chromosomes in the GnomAD database, including 247,866 homozygotes. 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: 𝑓 0.58 (25361 hom., cov: 35)
  • Exomes 𝑓: 0.56 (222505 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.0087198E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	NM_014291.4	MANE Select	c.115C>T	p.Arg39Cys	missense	Exon 1 of 9	NP_055106.1	O75600-1
	GCAT	NM_001171690.2		c.115C>T	p.Arg39Cys	missense	Exon 1 of 10	NP_001165161.1	O75600-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	ENST00000248924.11	TSL:1 MANE Select	c.115C>T	p.Arg39Cys	missense	Exon 1 of 9	ENSP00000248924.6	O75600-1
	GCAT	ENST00000892369.1		c.115C>T	p.Arg39Cys	missense	Exon 1 of 9	ENSP00000562428.1
	GCAT	ENST00000892367.1		c.115C>T	p.Arg39Cys	missense	Exon 1 of 9	ENSP00000562426.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87535 AN: 152074 Hom.: 25343 Cov.: 35

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.563 AC: 103442 AN: 183706 AF XY: 0.561

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.559 AC: 792213 AN: 1417554 Hom.: 222505 Cov.: 45 AF XY: 0.558 AC XY: 391710 AN XY: 701858

African (AFR) AF: 0.624 AC: 19492 AN: 31246

American (AMR) AF: 0.584 AC: 22588 AN: 38666

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 11724 AN: 25328

East Asian (EAS) AF: 0.621 AC: 22228 AN: 35782

South Asian (SAS) AF: 0.547 AC: 44187 AN: 80836

European-Finnish (FIN) AF: 0.583 AC: 29229 AN: 50166

Middle Eastern (MID) AF: 0.554 AC: 2955 AN: 5336

European-Non Finnish (NFE) AF: 0.556 AC: 606875 AN: 1091542

Other (OTH) AF: 0.562 AC: 32935 AN: 58652

GnomAD4 genome AF: 0.576 AC: 87605 AN: 152192 Hom.: 25361 Cov.: 35 AF XY: 0.575 AC XY: 42760 AN XY: 74414

African (AFR) AF: 0.615 AC: 25536 AN: 41534

American (AMR) AF: 0.572 AC: 8745 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3494 AN: 5168

South Asian (SAS) AF: 0.536 AC: 2591 AN: 4832

European-Finnish (FIN) AF: 0.589 AC: 6238 AN: 10590

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37729 AN: 67986

Other (OTH) AF: 0.558 AC: 1177 AN: 2108

Alfa AF: 0.559 Hom.: 17978

Bravo AF: 0.578

TwinsUK AF: 0.553 AC: 2050

ALSPAC AF: 0.557 AC: 2147

ESP6500AA AF: 0.614 AC: 2693

ESP6500EA AF: 0.546 AC: 4680

ExAC AF: 0.518 AC: 60249

Asia WGS AF: 0.590 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.000040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.049	D
Polyphen		0.096	B
Vest4		0.29
MPC		0.26
ClinPred		0.073	T
GERP RS		4.6
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.78
gMVP		0.44
Mutation Taster		=85/15	polymorphism (auto)

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; COSMIC: COSV50649782; COSMIC: COSV50649782;