rs2285179

Positions:

• chr22-37815947-G-A

Variant summary

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

The NM_014291.4(GCAT):​c.986+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,247,802 control chromosomes in the GnomAD database, including 199,805 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 0.55 (23164 hom., cov: 32)
  • Exomes 𝑓: 0.56 (176641 hom.)
• Consequence: GCAT NM_014291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCAT	NM_014291.4	c.986+113G>A		intron_variant		ENST00000248924.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCAT	ENST00000248924.11	c.986+113G>A		intron_variant		1	NM_014291.4	P1
GCAT	ENST00000323205.10	c.1064+113G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83079 AN: 151810 Hom.: 23162 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.563 AC: 617071 AN: 1095874 Hom.: 176641 AF XY: 0.565 AC XY: 311108 AN XY: 550476

Gnomad4 AFR exome AF: 0.493

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.825

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.547 AC: 83116 AN: 151928 Hom.: 23164 Cov.: 32 AF XY: 0.549 AC XY: 40798 AN XY: 74284

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.537

Alfa AF: 0.544 Hom.: 27251

Bravo AF: 0.546

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.073
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99

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: rs2285179; hg19: chr22-38211954;