rs121964975
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_000170.3(GLDC):c.2267_2269del(p.Phe756del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GLDC
NM_000170.3 inframe_deletion
NM_000170.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.91
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 Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 7 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 1 uncertain in NM_000170.3
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000170.3. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 9-6554714-CAGA-C is Pathogenic according to our data. Variant chr9-6554714-CAGA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56067.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-6554714-CAGA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.2267_2269del | p.Phe756del | inframe_deletion | 19/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.2267_2269del | p.Phe756del | inframe_deletion | 19/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250662Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135426
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460610Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726586
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Non-ketotic hyperglycinemia Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Glycine encephalopathy 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1992 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at