1-119711922-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000641597.1(PHGDH):c.-101G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,213,964 control chromosomes in the GnomAD database, including 317,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.76 ( 44369 hom., cov: 32)
Exomes 𝑓: 0.71 ( 272988 hom. )
Consequence
PHGDH
ENST00000641597.1 5_prime_UTR
ENST00000641597.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.563
Genes affected
PHGDH (HGNC:8923): (phosphoglycerate dehydrogenase) This gene encodes the enzyme which is involved in the early steps of L-serine synthesis in animal cells. L-serine is required for D-serine and other amino acid synthesis. The enzyme requires NAD/NADH as a cofactor and forms homotetramers for activity. Mutations in this gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. Multiple alternatively spliced transcript variants have been found, however the full-length nature of most are not known. [provided by RefSeq, Aug 2011]
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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=-0.87).
BP6
Variant 1-119711922-G-C is Benign according to our data. Variant chr1-119711922-G-C is described in ClinVar as [Benign]. Clinvar id is 292300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-119711922-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHGDH | NM_006623.4 | upstream_gene_variant | ENST00000641023.2 | ||||
PHGDH | XM_011541226.3 | upstream_gene_variant | |||||
PHGDH | XR_007058634.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHGDH | ENST00000641023.2 | upstream_gene_variant | NM_006623.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.757 AC: 115181AN: 152056Hom.: 44316 Cov.: 32
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GnomAD4 exome AF: 0.715 AC: 759073AN: 1061790Hom.: 272988 Cov.: 14 AF XY: 0.715 AC XY: 390416AN XY: 546254
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GnomAD4 genome AF: 0.758 AC: 115293AN: 152174Hom.: 44369 Cov.: 32 AF XY: 0.759 AC XY: 56431AN XY: 74376
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PHGDH deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2021 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Neu-Laxova syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at