Genetic Variant GLDC:c.2839-57A>G (chr9-6534845-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000170.3(GLDC):c.2839-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 900,590 control chromosomes in the GnomAD database, including 92,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14111 hom., cov: 32)

Exomes 𝑓: 0.45 ( 78755 hom. )

Consequence

GLDC
NM_000170.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-6534845-T-C is Benign according to our data. Variant chr9-6534845-T-C is described in ClinVar as [Benign]. Clinvar id is 1185161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-6534845-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDC	NM_000170.3 link	c.2839-57A>G		intron_variant	Intron 23 of 24	ENST00000321612.8	NP_000161.2	P23378

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8 link	c.2839-57A>G		intron_variant	Intron 23 of 24	1	NM_000170.3	ENSP00000370737.4		P23378

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64562

AN:

151866

Hom.:

14112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.406

GnomAD4 exome

AF:

0.455

AC:

340517

AN:

748606

Hom.:

78755

AF XY:

0.454

AC XY:

180623

AN XY:

397966

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.595

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.451

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.425

AC:

64587

AN:

151984

Hom.:

14111

Cov.:

AF XY:

0.428

AC XY:

31769

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.330

Gnomad4 EAS

AF:

0.491

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.432

Hom.:

14472

Bravo

AF:

0.427

Asia WGS

AF:

0.435

AC:

1514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Glycine encephalopathy

Benign:1

Jul 10, 2021

Genome-Nilou Lab

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

-0.89

CADD

Benign

0.23

DANN

Benign

0.46

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

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