rs760430736

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015891.3(CDC40):ā€‹c.659C>Gā€‹(p.Thr220Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,632 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

CDC40
NM_015891.3 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.48
Variant links:
Genes affected
CDC40 (HGNC:17350): (cell division cycle 40) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 rank MANE Protein UniProt
CDC40NM_015891.3 linkc.659C>G p.Thr220Arg missense_variant Exon 6 of 15 ENST00000307731.2 NP_056975.1 O60508
CDC40XM_047418862.1 linkc.-77C>G 5_prime_UTR_variant Exon 4 of 13 XP_047274818.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDC40ENST00000307731.2 linkc.659C>G p.Thr220Arg missense_variant Exon 6 of 15 1 NM_015891.3 ENSP00000304370.1 O60508
CDC40ENST00000368932.5 linkc.659C>G p.Thr220Arg missense_variant Exon 7 of 16 5 ENSP00000357928.1 O60508
CDC40ENST00000368930.5 linkc.659C>G p.Thr220Arg missense_variant Exon 6 of 15 2 ENSP00000357926.1 Q5SRN1
CDC40ENST00000606893.5 linkn.760C>G non_coding_transcript_exon_variant Exon 7 of 15 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000444
AC:
1
AN:
224988
Hom.:
0
AF XY:
0.00000818
AC XY:
1
AN XY:
122264
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000350
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.01e-7
AC:
1
AN:
1425632
Hom.:
0
Cov.:
28
AF XY:
0.00000141
AC XY:
1
AN XY:
708956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000258
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.093
T;T;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.44
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.91
N;N;N
REVEL
Benign
0.18
Sift
Benign
0.61
T;T;T
Sift4G
Benign
0.67
T;T;T
Polyphen
0.52
P;P;.
Vest4
0.66
MutPred
0.36
Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);
MVP
0.55
MPC
0.86
ClinPred
0.26
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs760430736; hg19: chr6-110531938; API