17-18333025-G-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004169.5(SHMT1):c.1054+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,087,362 control chromosomes in the GnomAD database, including 30,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.22 ( 3856 hom., cov: 33)
Exomes 𝑓: 0.24 ( 26622 hom. )
Consequence
SHMT1
NM_004169.5 intron
NM_004169.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.678
Genes affected
SHMT1 (HGNC:10850): (serine hydroxymethyltransferase 1) This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHMT1 | NM_004169.5 | c.1054+141C>T | intron_variant | ENST00000316694.8 | NP_004160.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHMT1 | ENST00000316694.8 | c.1054+141C>T | intron_variant | 1 | NM_004169.5 | ENSP00000318868 | P1 |
Frequencies
GnomAD3 genomes AF: 0.219 AC: 33336AN: 152122Hom.: 3850 Cov.: 33
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GnomAD3 exomes AF: 0.238 AC: 42390AN: 178122Hom.: 5142 AF XY: 0.237 AC XY: 22860AN XY: 96580
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GnomAD4 exome AF: 0.236 AC: 220722AN: 935122Hom.: 26622 Cov.: 12 AF XY: 0.235 AC XY: 113128AN XY: 482062
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GnomAD4 genome AF: 0.219 AC: 33360AN: 152240Hom.: 3856 Cov.: 33 AF XY: 0.218 AC XY: 16255AN XY: 74418
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
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