rs2228095

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000170.3(GLDC):c.660C>T(p.Leu220Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,605,400 control chromosomes in the GnomAD database, including 2,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 1112 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 978 hom. )

Consequence

GLDC
NM_000170.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.491

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 9-6606645-G-A is Benign according to our data. Variant chr9-6606645-G-A is described in ClinVar as [Benign]. Clinvar id is 367202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.491 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDC	NM_000170.3 link	c.660C>T	p.Leu220Leu	synonymous_variant	Exon 5 of 25	ENST00000321612.8	NP_000161.2	P23378

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8 link	c.660C>T	p.Leu220Leu	synonymous_variant	Exon 5 of 25	1	NM_000170.3	ENSP00000370737.4		P23378

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10074

AN:

152070

Hom.:

1089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0206

AC:

5181

AN:

251478

Hom.:

454

AF XY:

0.0173

AC XY:

2345

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.00795

AC:

11558

AN:

1453212

Hom.:

978

Cov.:

AF XY:

0.00762

AC XY:

5516

AN XY:

723642

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0131

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.000933

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000590

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0667

AC:

10149

AN:

152188

Hom.:

1112

Cov.:

AF XY:

0.0652

AC XY:

4850

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000971

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0294

Hom.:

226

Bravo

AF:

0.0751

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycine encephalopathy

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16601880) -

not specified

Benign:1

Jun 29, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.2

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over