9-6532510-TAA-T

Position:

• chr9-6532510-TAA-T

Variant summary

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

The NM_000170.3(GLDC):​c.*505_*506delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 143,780 control chromosomes in the GnomAD database, including 1,122 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1122 hom., cov: 22)
  • Exomes 𝑓: 0.12 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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]

GLDC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDC	NM_000170.3	c.*505_*506delTT		3_prime_UTR_variant	25/25	ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612	c.*505_*506delTT		3_prime_UTR_variant	25/25	1	NM_000170.3	ENSP00000370737.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 15676 AN: 143732 Hom.: 1126 Cov.: 22

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0684

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.124

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.118 AC: 500 AN: 4222 Hom.: 18 AF XY: 0.122 AC XY: 271 AN XY: 2216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.0940

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.109 AC: 15658 AN: 143780 Hom.: 1122 Cov.: 22 AF XY: 0.115 AC XY: 8037 AN XY: 69812

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.122

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Non-ketotic hyperglycinemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;