16-81082981-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004483.5(GCSH):c.425-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000843 in 1,423,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
GCSH
NM_004483.5 intron
NM_004483.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0290
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 16-81082981-C-T is Benign according to our data. Variant chr16-81082981-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1593641.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GCSH | NM_004483.5 | c.425-18G>A | intron_variant | ENST00000315467.9 | NP_004474.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GCSH | ENST00000315467.9 | c.425-18G>A | intron_variant | 1 | NM_004483.5 | ENSP00000319531.3 | ||||
ENSG00000284512 | ENST00000640345.1 | c.424+1482G>A | intron_variant | 5 | ENSP00000492798.1 | |||||
ENSG00000260643 | ENST00000564536.2 | c.424+1482G>A | intron_variant | 5 | ENSP00000491651.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 27
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251018Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135694
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GnomAD4 exome AF: 0.00000551 AC: 7AN: 1271562Hom.: 0 Cov.: 20 AF XY: 0.00000623 AC XY: 4AN XY: 642464
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152306Hom.: 0 Cov.: 27 AF XY: 0.0000269 AC XY: 2AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glycine encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 11, 2020 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
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