CFAP65

protein-coding

cilia and flagella associated protein 65, the group of Cilia and flagella associated

Gene summary

The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. The chicken ortholog of this gene is involved in the Rose-comb mutation, which is a large chromosome inversion, resulting in altered comb morphology and defects in sperm motility. [provided by RefSeq, Aug 2016]

Previous symbols:

CCDC108

MANE transcript

NM_194302.4

Inheritance

ClinVar variants

P:11U:44B:40

Top phenotype

Spermatogenic failure 40

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr2:219,002,846-219,041,527

External References & Databases

Ensembl (ENSG00000181378)

Transcript & Mutation Effects

hg38 • Region Span ~38.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 40LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032859

Submitter: Ambry Genetics

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 40AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30686508; 31413122; 31571197

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP65 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 40

Spermatogenic failure 40Total: 12

CFAP65-related disorderTotal: 4

Prostate cancerTotal: 1

Susceptibility to severe COVID-19Total: 1

Non-syndromic male infertility due to sperm motility disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194302.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	25 clinvar	1 clinvar	27
missense			42 clinvar	11 clinvar	3 clinvar	56
nonsense	5 clinvar	2 clinvar				7
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	7	4	44	36	4	95

Highest pathogenic variant AF is 0.000014868839

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194302.4	RefSeq	NP_919278.2	33	MANE Select
ENST00000341552.10	Ensembl	ENSP00000340776.5	33	MANE Select
NM_001278295.1	RefSeq	NP_001265224.1	13	Standard
NM_001278296.2	RefSeq	NP_001265225.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

RNA binding

Cellular Component

plasma membrane
integral component of membrane
motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341552
Coding exons: 33
Length: 38682
Individuals with no LoFs: 125465
Homozygous LoFs: 0
Heterozygous LoFs: 283
Defined: 125748
p: 0.00113

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.315	1069	1.10e+3	0.973	0.0000621	12612
Missense (PolyPhen)		292	305.12	0.957		3548
Synonymous	0.00275	463	463	1.00	0.0000283	3770
Loss of Function	3.29	57	90.8	0.628	0.00000439	1022

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0011	notable
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.00061	0.00060	rare
Finnish	0.00052	0.00051	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.0012	0.0011	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in sperm motility. {ECO:0000250|UniProtKB:I6WQT8}.;

Intolerance Scores

RVIS EVS: -1.85
RVIS percentile EVS: 2.04

Essentials

Essential (gene trap): N