rs1821892

chr9-6616648-C-G

Variant summary

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

The NM_000170.3(GLDC):c.470+3536G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,126 control chromosomes in the GnomAD database, including 4,636 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 0.23 (4636 hom., cov: 32)
• Consequence: GLDC NM_000170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDC	NM_000170.3	c.470+3536G>C		intron_variant		ENST00000321612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDC	ENST00000321612.8	c.470+3536G>C		intron_variant		1	NM_000170.3	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34706 AN: 152008 Hom.: 4620 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.229 AC: 34765 AN: 152126 Hom.: 4636 Cov.: 32 AF XY: 0.231 AC XY: 17191 AN XY: 74374

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.218

Alfa AF: 0.184 Hom.: 390

Bravo AF: 0.241

Asia WGS AF: 0.288 AC: 1000 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.36
Dann	Benign	0.54

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: rs1821892; hg19: chr9-6616648;