PMS1

PMS1 homolog 1, mismatch repair system component, the group of MutL homologs

Basic information

Region (hg38): 2:189784084-189877629

Previous symbols: [ "PMSL1" ]

Links

ENSG00000064933 ∙ NCBI:5378 ∙ OMIM:600258 ∙ HGNC:9121 ∙ Uniprot:P54277 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lynch syndrome (Refuted Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PMS1 gene.

• not provided (37 variants)
• not specified (31 variants)
• Inborn genetic diseases (19 variants)
• Ovarian cancer (8 variants)
• Hereditary breast ovarian cancer syndrome (3 variants)
• PMS1-related breast cancer (2 variants)
• Lynch syndrome 1 (2 variants)
• Polyp of colon (2 variants)
• Hereditary nonpolyposis colorectal carcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMS1 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				3	4	7
missense		2	31	6	10	49
nonsense			4			4
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding			1		11	12
Total	0	2	38	9	25

Highest pathogenic variant AF is 0.0000525

Variants in PMS1

This is a list of pathogenic ClinVar variants found in the PMS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-189784312-C-T			Benign (Mar 03, 2015)
2-189784514-G-T			Benign (Mar 03, 2015)
2-189784590-G-C			Benign (Mar 03, 2015)
2-189784667-G-A			Benign (Jun 23, 2018)
2-189784669-T-C			Benign (Jun 23, 2018)
2-189791888-G-C		Polyp of colon	Uncertain significance (Aug 01, 2016)
2-189795777-T-C			Benign (Jun 28, 2018)
2-189795810-G-T		PMS1-related disorder	Benign (Sep 29, 2020)
2-189795810-GG-TA		not specified	not provided (Sep 19, 2013)
2-189795811-G-A		PMS1-related disorder	Benign/Likely benign (Sep 29, 2020)
2-189795860-C-T		not specified	Uncertain significance (Nov 01, 2022)
2-189795923-C-G		not specified • Ovarian cancer	Likely pathogenic (Jan 01, 2022)
2-189795957-G-A			Benign (Mar 03, 2015)
2-189805644-T-C			Likely benign (Feb 08, 2018)
2-189805665-C-G		not specified	not provided (Sep 19, 2013)
2-189805681-T-C			Benign (Dec 31, 2019)
2-189805813-TA-T		PMS1-related disorder	Likely benign (Oct 21, 2020)
2-189805813-T-TA			Benign (Aug 30, 2019)
2-189805832-G-A		not specified • PMS1-related disorder	Likely benign (Nov 02, 2022)
2-189817906-G-C			Benign (Jun 22, 2018)
2-189817925-A-G			Benign (Mar 03, 2015)
2-189818038-G-A		Lynch syndrome 1	Uncertain significance (Mar 27, 2020)
2-189818083-C-CA		not specified	not provided (Sep 19, 2013)
2-189818098-A-G			Uncertain significance (-)
2-189818105-A-G		not specified	Uncertain significance (Aug 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMS1	protein_coding	protein_coding	ENST00000441310	12	93249

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.32e-17	0.256	125611	0	137	125748	0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.625	441	479	0.920	0.0000234	6190
Missense in Polyphen		139	143.94	0.9657		1800
Synonymous	1.61	141	167	0.842	0.00000861	1669
Loss of Function	1.48	32	42.4	0.755	0.00000225	568

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00150	0.00149
Ashkenazi Jewish	0.00229	0.00228
East Asian	0.000164	0.000163
Finnish	0.0000931	0.0000924
European (Non-Finnish)	0.000469	0.000466
Middle Eastern	0.000164	0.000163
South Asian	0.000459	0.000425
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably involved in the repair of mismatches in DNA. {ECO:0000269|PubMed:10748105}.

Recessive Scores

• pRec: 0.0919

Intolerance Scores

• loftool: 0.0827
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.32

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.470
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.247

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pms1

Gene ontology

• Biological process: mismatch repair;response to drug
• Cellular component: nucleus;mismatch repair complex;MutLalpha complex
• Molecular function: DNA binding;ATP binding;ATPase activity;enzyme binding;mismatched DNA binding