rs8177909
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004483.5(GCSH):c.292+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00097 in 1,572,096 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0053 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 7 hom. )
Consequence
GCSH
NM_004483.5 intron
NM_004483.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.675
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 16-81087592-A-C is Benign according to our data. Variant chr16-81087592-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 462904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00526 (801/152222) while in subpopulation AFR AF= 0.0186 (773/41518). AF 95% confidence interval is 0.0175. There are 8 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GCSH | NM_004483.5 | c.292+9T>G | intron_variant | ENST00000315467.9 | NP_004474.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GCSH | ENST00000315467.9 | c.292+9T>G | intron_variant | 1 | NM_004483.5 | ENSP00000319531.3 | ||||
ENSG00000284512 | ENST00000640345.1 | c.292+9T>G | intron_variant | 5 | ENSP00000492798.1 | |||||
ENSG00000260643 | ENST00000564536.2 | c.292+9T>G | intron_variant | 5 | ENSP00000491651.1 |
Frequencies
GnomAD3 genomes AF: 0.00527 AC: 802AN: 152108Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00142 AC: 356AN: 251184Hom.: 6 AF XY: 0.00111 AC XY: 151AN XY: 135828
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GnomAD4 exome AF: 0.000510 AC: 724AN: 1419874Hom.: 7 Cov.: 28 AF XY: 0.000455 AC XY: 323AN XY: 709166
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GnomAD4 genome AF: 0.00526 AC: 801AN: 152222Hom.: 8 Cov.: 32 AF XY: 0.00525 AC XY: 391AN XY: 74442
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glycine encephalopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
GCSH-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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