rs12004478

Positions:

• chr9-6581660-T-C

Variant summary

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

The ENST00000321612.8(GLDC):​c.1850+5481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,020 control chromosomes in the GnomAD database, including 5,845 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 0.27 (5845 hom., cov: 32)
• Consequence: GLDC ENST00000321612.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

GLDC (HGNC:4313): (glycine decarboxylase) Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the P protein, which binds to glycine and enables the methylamine group from glycine to be transferred to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH).[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDC	NM_000170.3	c.1850+5481A>G		intron_variant		ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8	c.1850+5481A>G		intron_variant		1	NM_000170.3	ENSP00000370737	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41621 AN: 151902 Hom.: 5850 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.274 AC: 41624 AN: 152020 Hom.: 5845 Cov.: 32 AF XY: 0.274 AC XY: 20358 AN XY: 74316

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.282

Alfa AF: 0.270 Hom.: 757

Bravo AF: 0.278

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.3
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs12004478; hg19: chr9-6581660;