Genetic Variant CCDC42:p.Trp303Ser (chr17-8730173-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144681.3(CCDC42):c.908G>C(p.Trp303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC42
NM_144681.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.750

Variant links:

Genes affected

CCDC42 (HGNC:26528): (coiled-coil domain containing 42) Predicted to be involved in spermatid development. [provided by Alliance of Genome Resources, Apr 2022]

CCDC42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30999434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC42	NM_144681.3 link	c.908G>C	p.Trp303Ser	missense_variant	Exon 7 of 7	ENST00000293845.8	NP_653282.2
CCDC42	NM_001158261.2 link	c.686G>C	p.Trp229Ser	missense_variant	Exon 6 of 6		NP_001151733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC42	ENST00000293845.8 link	c.908G>C	p.Trp303Ser	missense_variant	Exon 7 of 7	2	NM_144681.3	ENSP00000293845.3		Q96M95-1
CCDC42	ENST00000539522.2 link	c.686G>C	p.Trp229Ser	missense_variant	Exon 6 of 6	1		ENSP00000444359.2		Q96M95-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727182

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.908G>C (p.W303S) alteration is located in exon 7 (coding exon 7) of the CCDC42 gene. This alteration results from a G to C substitution at nucleotide position 908, causing the tryptophan (W) at amino acid position 303 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.22

Sift

Benign

0.38

T;D

Sift4G

Benign

0.41

T;T

Polyphen

1.0

D;.

Vest4

0.39

MutPred

0.56

Gain of disorder (P = 3e-04);.;

MVP

0.33

MPC

1.3

ClinPred

0.90

GERP RS

5.3

Varity_R

0.21

gMVP

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over