22-37815947-G-A

Variant names:

• chr22-37815947-G-A
• rs2285179
• NM_014291.4:c.986+113G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 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.986+113G>A		intron	N/A	NP_055106.1
	GCAT	NM_001171690.2		c.1064+113G>A		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.986+113G>A		intron	N/A	ENSP00000248924.6
	GCAT	ENST00000323205.10	TSL:2	c.1064+113G>A		intron	N/A	ENSP00000371110.3

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

African (AFR) AF: 0.493 AC: 12762 AN: 25892

American (AMR) AF: 0.572 AC: 19258 AN: 33664

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 9735 AN: 19420

East Asian (EAS) AF: 0.825 AC: 30985 AN: 37568

South Asian (SAS) AF: 0.632 AC: 42838 AN: 67768

European-Finnish (FIN) AF: 0.563 AC: 25697 AN: 45648

Middle Eastern (MID) AF: 0.556 AC: 1949 AN: 3506

European-Non Finnish (NFE) AF: 0.548 AC: 446959 AN: 814932

Other (OTH) AF: 0.566 AC: 26888 AN: 47476

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

African (AFR) AF: 0.491 AC: 20321 AN: 41410

American (AMR) AF: 0.559 AC: 8539 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1720 AN: 3468

East Asian (EAS) AF: 0.861 AC: 4456 AN: 5174

South Asian (SAS) AF: 0.629 AC: 3028 AN: 4812

European-Finnish (FIN) AF: 0.558 AC: 5902 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37411 AN: 67914

Other (OTH) AF: 0.537 AC: 1134 AN: 2110

Alfa AF: 0.543 Hom.: 34312

Bravo AF: 0.546

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.073
DANN	Benign	0.38
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
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: rs2285179; hg19: chr22-38211954;