NM_001164496.2:c.2005_2006delAT
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001164496.2(CFAP44):c.2005_2006delAT(p.Met669ValfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000439 in 1,593,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
CFAP44
NM_001164496.2 frameshift
NM_001164496.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.91
Publications
2 publications found
Genes affected
CFAP44 (HGNC:25631): (cilia and flagella associated protein 44) Enables peptidase activity. Involved in sperm axoneme assembly. Acts upstream of or within microtubule cytoskeleton organization. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Implicated in spermatogenic failure 20. [provided by Alliance of Genome Resources, Apr 2022]
CFAP44 Gene-Disease associations (from GenCC):
- spermatogenic failure 20Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
- non-syndromic male infertility due to sperm motility disorderInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-113380944-CAT-C is Pathogenic according to our data. Variant chr3-113380944-CAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 430938.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001164496.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CFAP44 | NM_001164496.2 | MANE Select | c.2005_2006delAT | p.Met669ValfsTer13 | frameshift | Exon 16 of 35 | NP_001157968.1 | ||
| CFAP44 | NM_018338.3 | c.2005_2006delAT | p.Met669ValfsTer13 | frameshift | Exon 16 of 21 | NP_060808.2 | |||
| SPICE1-CFAP44 | NR_183045.1 | n.4885_4886delAT | non_coding_transcript_exon | Exon 31 of 49 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CFAP44 | ENST00000393845.9 | TSL:5 MANE Select | c.2005_2006delAT | p.Met669ValfsTer13 | frameshift | Exon 16 of 35 | ENSP00000377428.2 | ||
| CFAP44 | ENST00000295868.6 | TSL:1 | c.2005_2006delAT | p.Met669ValfsTer13 | frameshift | Exon 16 of 21 | ENSP00000295868.2 | ||
| SPICE1-CFAP44 | ENST00000649772.1 | n.*2170_*2171delAT | non_coding_transcript_exon | Exon 35 of 39 | ENSP00000497606.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152106
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000832 AC: 2AN: 240364 AF XY: 0.00000769 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
240364
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000347 AC: 5AN: 1441448Hom.: 0 AF XY: 0.00000419 AC XY: 3AN XY: 716462 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1441448
Hom.:
AF XY:
AC XY:
3
AN XY:
716462
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32904
American (AMR)
AF:
AC:
0
AN:
42542
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25602
East Asian (EAS)
AF:
AC:
0
AN:
38618
South Asian (SAS)
AF:
AC:
0
AN:
81494
European-Finnish (FIN)
AF:
AC:
1
AN:
52730
Middle Eastern (MID)
AF:
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1102406
Other (OTH)
AF:
AC:
0
AN:
59464
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74436 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152224
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74436
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41550
American (AMR)
AF:
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10584
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Spermatogenic failure 20 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.