22-37809053-A-G

Position:

• chr22-37809053-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014291.4(GCAT):​c.196+890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,254 control chromosomes in the GnomAD database, including 57,664 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 0.87 (57664 hom., cov: 33)
• Consequence: GCAT NM_014291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCAT	NM_014291.4	c.196+890A>G		intron_variant		ENST00000248924.11	NP_055106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCAT	ENST00000248924.11	c.196+890A>G		intron_variant		1	NM_014291.4	ENSP00000248924.6

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132258 AN: 152136 Hom.: 57629 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.868

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.869 AC: 132351 AN: 152254 Hom.: 57664 Cov.: 33 AF XY: 0.872 AC XY: 64949 AN XY: 74444

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.869

Alfa AF: 0.869 Hom.: 14669

Bravo AF: 0.868

Asia WGS AF: 0.944 AC: 3281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.49

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: rs763137; hg19: chr22-38205060;