22-37809053-A-G

Variant names:

• chr22-37809053-A-G
• rs763137
• NM_014291.4:c.196+890A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	NM_014291.4	MANE Select	c.196+890A>G		intron	N/A	NP_055106.1
	GCAT	NM_001171690.2		c.196+890A>G		intron	N/A	NP_001165161.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCAT	ENST00000248924.11	TSL:1 MANE Select	c.196+890A>G		intron	N/A	ENSP00000248924.6
	GCAT	ENST00000323205.10	TSL:2	c.196+890A>G		intron	N/A	ENSP00000371110.3
	GCAT	ENST00000451984.1	TSL:3	c.148+890A>G		intron	N/A	ENSP00000388151.1

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

African (AFR) AF: 0.842 AC: 34962 AN: 41546

American (AMR) AF: 0.902 AC: 13803 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2907 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5145 AN: 5178

South Asian (SAS) AF: 0.905 AC: 4362 AN: 4818

European-Finnish (FIN) AF: 0.906 AC: 9612 AN: 10604

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58730 AN: 68012

Other (OTH) AF: 0.869 AC: 1837 AN: 2114

Alfa AF: 0.869 Hom.: 22940

Bravo AF: 0.868

Asia WGS AF: 0.944 AC: 3281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.49
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs763137; hg19: chr22-38205060;