SHMT1

serine hydroxymethyltransferase 1, the group of Serine hydroxymethyltransferase family|MicroRNA protein coding host genes

Basic information

Region (hg38): 17:18327859-18363563

Links

ENSG00000176974 ∙ NCBI:6470 ∙ OMIM:182144 ∙ HGNC:10850 ∙ Uniprot:P34896 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHMT1 gene.

• not provided (14 variants)
• Inborn genetic diseases (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHMT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			13	2	2	17
nonsense						0
start loss				1	1	2
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding					1	1
Total	0	0	13	4	7

Variants in SHMT1

This is a list of pathogenic ClinVar variants found in the SHMT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-18328769-G-C		not specified	Uncertain significance (Jul 19, 2023)
17-18328781-A-C		not specified	Uncertain significance (Aug 09, 2021)
17-18328782-G-A		Gastrointestinal stromal tumor	Uncertain significance (-)
17-18328822-G-A			Benign (Dec 31, 2019)
17-18328826-G-A		not specified	Uncertain significance (Jun 18, 2021)
17-18328861-C-A		not specified	Uncertain significance (Feb 05, 2024)
17-18328886-G-A		not specified	Likely benign (Feb 15, 2023)
17-18329356-G-A		not specified	Uncertain significance (Feb 26, 2024)
17-18329371-G-A		not specified	Uncertain significance (Nov 09, 2023)
17-18330591-C-A		not specified	Uncertain significance (Nov 07, 2022)
17-18333160-C-T			Likely benign (Dec 31, 2019)
17-18333174-A-G		not specified	Uncertain significance (Oct 03, 2022)
17-18333190-C-G		not specified	Uncertain significance (Dec 19, 2022)
17-18333202-C-G			Benign (Dec 31, 2019)
17-18333286-C-T		not specified	Uncertain significance (Jul 19, 2022)
17-18335565-T-C		not specified	Uncertain significance (Jun 06, 2023)
17-18335594-C-A		not specified	Uncertain significance (Oct 31, 2023)
17-18335678-G-A			Benign (Dec 31, 2019)
17-18340069-C-T		not specified	Uncertain significance (Jan 03, 2024)
17-18340084-G-A		not specified	Uncertain significance (Dec 15, 2023)
17-18340104-C-G			Benign (Jul 10, 2018)
17-18340104-C-T			Benign (Dec 05, 2018)
17-18340147-G-A		not specified	Likely benign (Jan 03, 2024)
17-18340157-C-T		not specified	Uncertain significance (Nov 14, 2023)
17-18340192-C-T		not specified	Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHMT1	protein_coding	protein_coding	ENST00000316694	11	35670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.27e-14	0.0233	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.352	259	275	0.940	0.0000168	3127
Missense in Polyphen		113	135.39	0.83462		1439
Synonymous	-0.661	125	116	1.08	0.00000744	983
Loss of Function	0.205	22	23.1	0.954	0.00000146	263

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00122	0.00122
Ashkenazi Jewish	0.000799	0.000794
East Asian	0.000544	0.000489
Finnish	0.000233	0.000231
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000544	0.000489
South Asian	0.000359	0.000359
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Interconversion of serine and glycine (PubMed:8505317, PubMed:24698160). {ECO:0000269|PubMed:24698160, ECO:0000269|PubMed:8505317}.
• Pathway: Antimetabolite Pathway - Folate Cycle, Pharmacodynamics;One carbon pool by folate - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Methotrexate Pathway (Cancer Cell), Pharmacodynamics;Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;3-Phosphoglycerate dehydrogenase deficiency;Carnitine Synthesis;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;sarcosine oncometabolite pathway ;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Cystathionine Beta-Synthase Deficiency;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Glycine Metabolism;Folate Metabolism;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;One carbon metabolism and related pathways;Pathways in clear cell renal cell carcinoma;folate polyglutamylation;Folate metabolism;Branched-chain amino acid catabolism;glycine/serine biosynthesis;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Lysine degradation;folate transformations I;glycine betaine degradation;Metabolism of folate and pterines;dTMP <i>de novo</i> biosynthesis (mitochondrial);Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;superpathway of choline degradation to L-serine;Lysine metabolism;Vitamin B9 (folate) metabolism;Carnitine synthesis;serine and glycine biosynthesis;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.940
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.38

Haploinsufficiency Scores

• pHI: 0.824
• hipred: Y
• hipred_score: 0.771
• ghis: 0.419

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Shmt1
• Phenotype: neoplasm; liver/biliary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: dTMP biosynthetic process;glycine metabolic process;L-serine metabolic process;L-serine catabolic process;one-carbon metabolic process;purine nucleobase biosynthetic process;negative regulation of translation;glycine biosynthetic process from serine;tetrahydrofolate interconversion;carnitine biosynthetic process;tetrahydrofolate metabolic process;folic acid metabolic process;protein tetramerization;protein homotetramerization;cellular response to tetrahydrofolate;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;cytosol;extracellular exosome
• Molecular function: translation repressor activity, mRNA regulatory element binding;glycine hydroxymethyltransferase activity;protein binding;zinc ion binding;L-allo-threonine aldolase activity;amino acid binding;pyridoxal phosphate binding;identical protein binding;protein homodimerization activity;mRNA 5'-UTR binding;cobalt ion binding;serine binding