HFM1

helicase for meiosis 1, the group of RNA helicases

Basic information

Region (hg38): 1:91260766-91404856

Previous symbols: [ "SEC63D1" ]

Links

ENSG00000162669 ∙ NCBI:164045 ∙ OMIM:615684 ∙ HGNC:20193 ∙ Uniprot:A2PYH4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility with azoospermia or oligozoospermia due to single gene mutation (Disputed Evidence), mode of inheritance: AR
• premature ovarian failure 9 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure 9	AR	Obstetric	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Obstetric	24597873

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HFM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HFM1 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	4	1	6
missense			60	6	4	70
nonsense						0
start loss		1				1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				4	1	5
non coding				2		2
Total	0	2	61	12	5

Variants in HFM1

This is a list of pathogenic ClinVar variants found in the HFM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-91261298-T-C		not specified	Uncertain significance (Jul 31, 2024)
1-91261300-C-T		not specified	Uncertain significance (Dec 05, 2024)
1-91261338-T-G		not specified	Uncertain significance (May 23, 2024)
1-91262277-A-T		not specified	Uncertain significance (Sep 12, 2023)
1-91262279-A-T		not specified	Uncertain significance (May 02, 2024)
1-91262316-T-C		not specified	Uncertain significance (Dec 03, 2021)
1-91262352-TC-T		-	no classification for the single variant (-)
1-91262365-T-G		not specified	Uncertain significance (Oct 26, 2022)
1-91262366-T-G		not specified	Uncertain significance (Nov 22, 2021)
1-91262505-AG-A		Premature ovarian failure 9	Uncertain significance (-)
1-91262569-G-A		not specified	Uncertain significance (Sep 26, 2023)
1-91266061-GG-C		Premature ovarian failure 9	Pathogenic (Mar 06, 2014)
1-91266111-T-A		not specified	Likely benign (Jan 23, 2018)
1-91267768-T-A		not specified	Uncertain significance (May 07, 2024)
1-91267806-A-T		not specified	Uncertain significance (Sep 27, 2022)
1-91267816-C-A		not specified	Uncertain significance (Jan 11, 2023)
1-91267840-T-G		not specified	Uncertain significance (Jan 07, 2022)
1-91273797-T-C		not specified	Uncertain significance (Jan 06, 2023)
1-91274758-G-C		not specified	Uncertain significance (Nov 06, 2023)
1-91274768-A-C		not specified	Uncertain significance (Feb 03, 2022)
1-91274787-C-T		not specified	Uncertain significance (Sep 22, 2023)
1-91276627-C-T		Azoospermia	Pathogenic (Dec 20, 2021)
1-91276683-G-C		not specified	Uncertain significance (Sep 22, 2023)
1-91276689-T-C		not specified	Uncertain significance (Apr 09, 2024)
1-91276702-T-C		not specified	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HFM1	protein_coding	protein_coding	ENST00000370425	38	144104

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.73e-32	0.0809	125603	0	137	125740	0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.742	627	682	0.920	0.0000319	9464
Missense in Polyphen		142	181.84	0.78089		2547
Synonymous	0.593	215	226	0.950	0.0000105	2551
Loss of Function	2.07	60	80.0	0.750	0.00000415	1083

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000768	0.000755
Ashkenazi Jewish	0.00	0.00
East Asian	0.000638	0.000598
Finnish	0.000696	0.000693
European (Non-Finnish)	0.000730	0.000704
Middle Eastern	0.000638	0.000598
South Asian	0.000407	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for crossover formation and complete synapsis of homologous chromosomes during meiosis. {ECO:0000250|UniProtKB:D3Z4R1}.

Intolerance Scores

• loftool: 0.986
• rvis_EVS: -0.72
• rvis_percentile_EVS: 14.27

Haploinsufficiency Scores

• pHI: 0.0728
• hipred: N
• hipred_score: 0.307
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.177

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hfm1
• Phenotype: endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: resolution of meiotic recombination intermediates
• Molecular function: nucleic acid binding;helicase activity;ATP binding