Variant rs11789777 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000321612.8(GLDC):c.1261+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,226,890 control chromosomes in the GnomAD database, including 40,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3903 hom., cov: 33)

Exomes 𝑓: 0.26 ( 36956 hom. )

Consequence

GLDC
ENST00000321612.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.839

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-6594978-T-C is Benign according to our data. Variant chr9-6594978-T-C is described in ClinVar as [Benign]. Clinvar id is 1185251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDC	NM_000170.3 linkuse as main transcript	c.1261+36A>G		intron_variant		ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8 linkuse as main transcript	c.1261+36A>G		intron_variant		1	NM_000170.3	ENSP00000370737	P1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32259

AN:

152080

Hom.:

3906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0927

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.238

GnomAD3 exomes

AF:

0.251

AC:

62950

AN:

250624

Hom.:

8343

AF XY:

0.253

AC XY:

34257

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.0903

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.258

AC:

277508

AN:

1074692

Hom.:

36956

Cov.:

AF XY:

0.260

AC XY:

143351

AN XY:

552068

show subpopulations

Gnomad4 AFR exome

AF:

0.0916

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.212

AC:

32255

AN:

152198

Hom.:

3903

Cov.:

AF XY:

0.213

AC XY:

15885

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.279

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.258

Hom.:

10934

Bravo

AF:

0.208

Asia WGS

AF:

0.201

AC:

700

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Non-ketotic hyperglycinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

DANN

Benign

0.78

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