NM_000170.3:c.106G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000170.3(GLDC):​c.106G>T​(p.Asp36Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D36H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

GLDC
NM_000170.3 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.803

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • glycine encephalopathy
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen
  • glycine encephalopathy 1
    Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
  • infantile glycine encephalopathy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • neonatal glycine encephalopathy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • atypical glycine encephalopathy
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20228818).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLDCNM_000170.3 linkc.106G>T p.Asp36Tyr missense_variant Exon 1 of 25 ENST00000321612.8 NP_000161.2 P23378

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLDCENST00000321612.8 linkc.106G>T p.Asp36Tyr missense_variant Exon 1 of 25 1 NM_000170.3 ENSP00000370737.4 P23378
LINC02851ENST00000813373.1 linkn.124+468C>A intron_variant Intron 1 of 2
LINC02851ENST00000813380.1 linkn.405+468C>A intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.38e-7
AC:
1
AN:
1354182
Hom.:
0
Cov.:
32
AF XY:
0.00000150
AC XY:
1
AN XY:
667736
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28026
American (AMR)
AF:
0.00
AC:
0
AN:
32058
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23762
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31274
South Asian (SAS)
AF:
0.0000133
AC:
1
AN:
75328
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42690
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3958
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1061000
Other (OTH)
AF:
0.00
AC:
0
AN:
56086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
20
DANN
Benign
0.95
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.47
T
M_CAP
Pathogenic
0.78
D
MetaRNN
Benign
0.20
T
MetaSVM
Uncertain
0.71
D
MutationAssessor
Benign
0.0
N
PhyloP100
0.80
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.070
N
REVEL
Uncertain
0.38
Sift
Benign
0.087
T
Sift4G
Benign
0.56
T
Polyphen
0.036
B
Vest4
0.24
MutPred
0.18
Gain of MoRF binding (P = 0.054);
MVP
0.90
MPC
0.060
ClinPred
0.12
T
GERP RS
2.7
PromoterAI
-0.028
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.056
gMVP
0.56
Mutation Taster
=94/6
polymorphism

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

Other links and lift over

dbSNP: rs573883784; hg19: chr9-6645394; API