rs386833573

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_000170.3(GLDC):​c.2896A>G​(p.Arg966Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

GLDC
NM_000170.3 missense

Scores

12
6
1

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.25
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.863
PP5
Variant 9-6534731-T-C is Pathogenic according to our data. Variant chr9-6534731-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56091.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-6534731-T-C is described in Lovd as [Pathogenic]. Variant chr9-6534731-T-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLDCNM_000170.3 linkuse as main transcriptc.2896A>G p.Arg966Gly missense_variant 24/25 ENST00000321612.8 NP_000161.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLDCENST00000321612.8 linkuse as main transcriptc.2896A>G p.Arg966Gly missense_variant 24/251 NM_000170.3 ENSP00000370737 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Non-ketotic hyperglycinemia Pathogenic:1
Likely pathogenic, no assertion criteria providedliterature onlyJuha Muilu Group; Institute for Molecular Medicine Finland (FIMM)-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.82
D;.;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Pathogenic
0.52
D
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Uncertain
0.75
D
MutationAssessor
Pathogenic
3.8
H;.;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-6.3
D;.;.;.
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D;.;.;.
Sift4G
Pathogenic
0.0
D;.;.;.
Polyphen
1.0
D;.;.;.
Vest4
0.96
MutPred
0.59
Loss of solvent accessibility (P = 0.0329);.;.;.;
MVP
0.95
MPC
0.31
ClinPred
1.0
D
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.97
gMVP
0.96

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.

Other links and lift over

dbSNP: rs386833573; hg19: chr9-6534731; API