rs76447100
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006623.4(PHGDH):c.357-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,611,976 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0080 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 19 hom. )
Consequence
PHGDH
NM_006623.4 splice_polypyrimidine_tract, intron
NM_006623.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.66
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=-0.67).
BP6
?
Variant 1-119726834-T-C is Benign according to our data. Variant chr1-119726834-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445502.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 = 0.00796 (1212/152322) while in subpopulation AFR AF= 0.0278 (1155/41560). AF 95% confidence interval is 0.0265. There are 15 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHGDH | NM_006623.4 | c.357-17T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000641023.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHGDH | ENST00000641023.2 | c.357-17T>C | splice_polypyrimidine_tract_variant, intron_variant | NM_006623.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00794 AC: 1208AN: 152204Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00211 AC: 530AN: 251432Hom.: 7 AF XY: 0.00152 AC XY: 207AN XY: 135902
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GnomAD4 exome AF: 0.000789 AC: 1151AN: 1459654Hom.: 19 Cov.: 30 AF XY: 0.000709 AC XY: 515AN XY: 726284
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ClinVar
Significance: Benign/Likely 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 | Apr 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 24, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2021 | - - |
Neu-Laxova syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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