Genetic Variant GCAT:p.Arg39Cys (chr22-37808082-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.58 ( 25361 hom., cov: 35)

Exomes 𝑓: 0.56 ( 222505 hom. )

Consequence

GCAT
NM_014291.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.86

Variant links:

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]

GCAT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCAT	NM_014291.4 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 1 of 9	ENST00000248924.11	NP_055106.1	O75600-1A8K228

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCAT	ENST00000248924.11 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 1 of 9	1	NM_014291.4	ENSP00000248924.6		O75600-1

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87535

AN:

152074

Hom.:

25343

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.563

AC:

103442

AN:

183706

Hom.:

29231

AF XY:

0.561

AC XY:

55618

AN XY:

99178

show subpopulations

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 SAS exome

AF:

0.545

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.:

AF XY:

0.558

AC XY:

391710

AN XY:

701858

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.584

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.547

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.576

AC:

87605

AN:

152192

Hom.:

25361

Cov.:

AF XY:

0.575

AC XY:

42760

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.572

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.676

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.558

Alfa

AF:

0.554

Hom.:

12915

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.000040

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

M;M;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.049

D;D;T

Polyphen

0.096

.;B;.

Vest4

0.29

MPC

0.26

ClinPred

0.073

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.78

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over