rs10975641

Positions:

• chr9-6556839-C-G
• chr9-6556839-C-T

Variant summary

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

The NM_000170.3(GLDC):​c.2053-537G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,602 control chromosomes in the GnomAD database, including 10,206 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 0.36 (10206 hom., cov: 31)
• Consequence: GLDC NM_000170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDC	NM_000170.3	c.2053-537G>C		intron_variant		ENST00000321612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDC	ENST00000321612.8	c.2053-537G>C		intron_variant		1	NM_000170.3	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55167 AN: 151488 Hom.: 10197 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.364 AC: 55198 AN: 151602 Hom.: 10206 Cov.: 31 AF XY: 0.364 AC XY: 26955 AN XY: 74042

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.363

Alfa AF: 0.334 Hom.: 1053

Bravo AF: 0.367

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.39

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: rs10975641; hg19: chr9-6556839;