9-6532510-TAAA-TAAAA

Variant names:

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

Variant summary

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

The NM_000170.3(GLDC):​c.*506dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 147,924 control chromosomes in the GnomAD database, including 348 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (348 hom., cov: 22)
  • Exomes 𝑓: 0.074 (0 hom.)
• 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 (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5520 AN: 143692 Hom.: 347 Cov.: 22

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000798

Gnomad SAS AF: 0.000662

Gnomad FIN AF: 0.00206

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.0262

GnomAD4 exome AF: 0.0736 AC: 308 AN: 4184 Hom.: 0 Cov.: 0 AF XY: 0.0721 AC XY: 158 AN XY: 2190

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0809

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0185

Gnomad4 SAS exome AF: 0.0694

Gnomad4 FIN exome AF: 0.0219

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.0384 AC: 5521 AN: 143740 Hom.: 348 Cov.: 22 AF XY: 0.0373 AC XY: 2603 AN XY: 69782

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.000800

Gnomad4 SAS AF: 0.000443

Gnomad4 FIN AF: 0.00206

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.0260

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;