10-104380180-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001008723.2(CFAP58):c.1325G>A(p.Arg442His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
CFAP58
NM_001008723.2 missense
NM_001008723.2 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 9.85
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.1325G>A | p.Arg442His | missense_variant | 9/18 | ENST00000369704.8 | |
CFAP58 | NM_001400226.1 | c.1271G>A | p.Arg424His | missense_variant | 10/19 | ||
CFAP58 | NM_001400227.1 | c.1271G>A | p.Arg424His | missense_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP58 | ENST00000369704.8 | c.1325G>A | p.Arg442His | missense_variant | 9/18 | 1 | NM_001008723.2 | P1 | |
CFAP58 | ENST00000369703.1 | c.191G>A | p.Arg64His | missense_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152180Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251208Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135762
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GnomAD4 exome AF: 0.000246 AC: 359AN: 1461794Hom.: 0 Cov.: 30 AF XY: 0.000243 AC XY: 177AN XY: 727192
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74342
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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 | Aug 10, 2021 | The c.1325G>A (p.R442H) alteration is located in exon 9 (coding exon 9) of the CFAP58 gene. This alteration results from a G to A substitution at nucleotide position 1325, causing the arginine (R) at amino acid position 442 to be replaced by a histidine (H). 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
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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