9-6532510-TAAA-TAA

Variant names:

• chr9-6532510-TA-T
• rs3215922
• NM_000170.3:c.*506delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000170.3(GLDC):​c.*506delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 143,666 control chromosomes in the GnomAD database, including 702 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (702 hom., cov: 22)
  • Exomes 𝑓: 0.15 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDC	NM_000170.3	c.*506delT		3_prime_UTR_variant	Exon 25 of 25	ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612	c.*506delT		3_prime_UTR_variant	Exon 25 of 25	1	NM_000170.3	ENSP00000370737.4

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 13621 AN: 143618 Hom.: 701 Cov.: 22

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0933

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0879

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.155 AC: 640 AN: 4134 Hom.: 2 Cov.: 0 AF XY: 0.147 AC XY: 320 AN XY: 2172

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0769

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.0949 AC: 13631 AN: 143666 Hom.: 702 Cov.: 22 AF XY: 0.0926 AC XY: 6460 AN XY: 69734

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.0755

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3215922; hg19: chr9-6532510;