Genetic Variant NM_015891.3:c.107C>G (chr6-110180551-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015891.3(CDC40):c.107C>G(p.Ser36Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CDC40
NM_015891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

Publications

0 publications found

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]

CDC40 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 15
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

CDC40 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22221363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015891.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC40	NM_015891.3	MANE Select	c.107C>G	p.Ser36Cys	missense	Exon 1 of 15	NP_056975.1	O60508

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC40	ENST00000307731.2	TSL:1 MANE Select	c.107C>G	p.Ser36Cys	missense	Exon 1 of 15	ENSP00000304370.1	O60508
CDC40	ENST00000924587.1		c.107C>G	p.Ser36Cys	missense	Exon 1 of 15	ENSP00000594646.1
CDC40	ENST00000368932.5	TSL:5	c.107C>G	p.Ser36Cys	missense	Exon 2 of 16	ENSP00000357928.1	O60508

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

Eigen

Benign

-0.039

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.80

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

4.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

REVEL

Benign

0.20

Sift

Benign

0.096

Sift4G

Benign

0.065

Polyphen

0.0

Vest4

0.46

MutPred

0.24

Gain of catalytic residue at L37 (P = 0.0135)

MVP

0.56

MPC

0.67

ClinPred

0.75

GERP RS

5.5

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.36

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over