rs8177876
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_004483.5(GCSH):c.159C>T(p.Phe53=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0657 in 1,609,126 control chromosomes in the GnomAD database, including 4,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.057 ( 257 hom., cov: 32)
Exomes 𝑓: 0.067 ( 3785 hom. )
Consequence
GCSH
NM_004483.5 synonymous
NM_004483.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.11
Genes affected
GCSH (HGNC:4208): (glycine cleavage system protein H) 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 H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 16-81090670-G-A is Benign according to our data. Variant chr16-81090670-G-A is described in ClinVar as [Benign]. Clinvar id is 1166773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81090670-G-A is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCSH | NM_004483.5 | c.159C>T | p.Phe53= | synonymous_variant | 2/5 | ENST00000315467.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCSH | ENST00000315467.9 | c.159C>T | p.Phe53= | synonymous_variant | 2/5 | 1 | NM_004483.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0571 AC: 8686AN: 152074Hom.: 255 Cov.: 32
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GnomAD3 exomes AF: 0.0540 AC: 13570AN: 251404Hom.: 527 AF XY: 0.0541 AC XY: 7357AN XY: 135900
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GnomAD4 exome AF: 0.0666 AC: 96966AN: 1456934Hom.: 3785 Cov.: 29 AF XY: 0.0652 AC XY: 47297AN XY: 725144
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GnomAD4 genome ? AF: 0.0572 AC: 8698AN: 152192Hom.: 257 Cov.: 32 AF XY: 0.0575 AC XY: 4279AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Non-ketotic hyperglycinemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at