rs73089095

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194302.4(CFAP65):​c.5415G>C​(p.Lys1805Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K1805K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CFAP65
NM_194302.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.410
Variant links:
Genes affected
CFAP65 (HGNC:25325): (cilia and flagella associated protein 65) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053031683).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFAP65NM_194302.4 linkc.5415G>C p.Lys1805Asn missense_variant Exon 33 of 35 ENST00000341552.10 NP_919278.2 Q6ZU64-1B4DZ05

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFAP65ENST00000341552.10 linkc.5415G>C p.Lys1805Asn missense_variant Exon 33 of 35 5 NM_194302.4 ENSP00000340776.5 Q6ZU64-1
CFAP65ENST00000453220.5 linkc.5415G>C p.Lys1805Asn missense_variant Exon 31 of 33 5 ENSP00000409117.1 Q6ZU64-1
ENSG00000224090ENST00000441450.1 linkn.86+1792C>G intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251276
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461746
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
11
DANN
Benign
0.90
DEOGEN2
Benign
0.018
T;T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.28
.;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.88
N;N
REVEL
Benign
0.020
Sift
Benign
0.26
T;T
Sift4G
Uncertain
0.010
D;D
Polyphen
0.0010
B;B
Vest4
0.20
MutPred
0.20
Loss of methylation at K1805 (P = 0.0015);Loss of methylation at K1805 (P = 0.0015);
MVP
0.099
MPC
0.082
ClinPred
0.047
T
GERP RS
1.6
Varity_R
0.059
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73089095; hg19: chr2-219868814; API