10-104380183-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001008723.2(CFAP58):c.1328A>G(p.Asp443Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CFAP58
NM_001008723.2 missense
NM_001008723.2 missense
Scores
4
10
4
Clinical Significance
Conservation
PhyloP100: 9.19
Genes affected
CFAP58 (HGNC:26676): (cilia and flagella associated protein 58) Involved in protein localization to motile cilium; sperm axoneme assembly; and sperm mitochondrial sheath assembly. Located in sperm midpiece. Implicated in spermatogenic failure 49. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP58 | NM_001008723.2 | c.1328A>G | p.Asp443Gly | missense_variant | 9/18 | ENST00000369704.8 | |
CFAP58 | NM_001400226.1 | c.1274A>G | p.Asp425Gly | missense_variant | 10/19 | ||
CFAP58 | NM_001400227.1 | c.1274A>G | p.Asp425Gly | missense_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP58 | ENST00000369704.8 | c.1328A>G | p.Asp443Gly | missense_variant | 9/18 | 1 | NM_001008723.2 | P1 | |
CFAP58 | ENST00000369703.1 | c.194A>G | p.Asp65Gly | missense_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251210Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135772
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461774Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727190
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The c.1328A>G (p.D443G) alteration is located in exon 9 (coding exon 9) of the CFAP58 gene. This alteration results from a A to G substitution at nucleotide position 1328, causing the aspartic acid (D) at amino acid position 443 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at