rs7848919

chr9-6532477-G-Achr9-6532477-G-Cchr9-6532477-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000170.3(GLDC):c.*540C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 154,584 control chromosomes in the GnomAD database, including 38,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38283 hom., cov: 29)
  • Exomes 𝑓: 0.63 (673 hom.)
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-6532477-G-A is Benign according to our data. Variant chr9-6532477-G-A is described in ClinVar as [Benign]. Clinvar id is 367162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDC	NM_000170.3	c.*540C>T		3_prime_UTR_variant	25/25	ENST00000321612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDC	ENST00000321612.8	c.*540C>T		3_prime_UTR_variant	25/25	1	NM_000170.3	P1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107145 AN: 151230 Hom.: 38254 Cov.: 29

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.629 AC: 2041 AN: 3246 Hom.: 673 Cov.: 0 AF XY: 0.628 AC XY: 1092 AN XY: 1738

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.585

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.709 AC: 107227 AN: 151338 Hom.: 38283 Cov.: 29 AF XY: 0.715 AC XY: 52828 AN XY: 73900

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.680

Alfa AF: 0.683 Hom.: 53038

Bravo AF: 0.706

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-ketotic hyperglycinemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.2
Dann	Benign	0.62

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: rs7848919; hg19: chr9-6532477;