9-6643754-T-C

Position:

• chr9-6643754-T-C

Variant summary

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

The NM_000170.3(GLDC):​c.334+860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,414 control chromosomes in the GnomAD database, including 7,963 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 0.31 (7963 hom., cov: 29)
• Consequence: GLDC NM_000170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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]

GLDC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDC	NM_000170.3	c.334+860A>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.334+860A>G		intron_variant		1	NM_000170.3	ENSP00000370737.4
GLDC	ENST00000639364.1	n.34+777A>G		intron_variant		5
GLDC	ENST00000639954.1	n.178+860A>G		intron_variant		5
GLDC	ENST00000640592.1	n.217+860A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47116 AN: 151302 Hom.: 7951 Cov.: 29

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.311 AC: 47152 AN: 151414 Hom.: 7963 Cov.: 29 AF XY: 0.315 AC XY: 23329 AN XY: 73952

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.310

Alfa AF: 0.258 Hom.: 873

Bravo AF: 0.329

Asia WGS AF: 0.424 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.20

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: rs1755615; hg19: chr9-6643754; COSMIC: COSV58678149; COSMIC: COSV58678149;