17-8743688-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144681.3(CCDC42):c.232G>C(p.Glu78Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC42 NM_144681.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23061496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC42	NM_144681.3	c.232G>C	p.Glu78Gln	missense_variant	3/7	ENST00000293845.8
CCDC42	NM_001158261.2	c.232G>C	p.Glu78Gln	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC42	ENST00000293845.8	c.232G>C	p.Glu78Gln	missense_variant	3/7	2	NM_144681.3	P1
CCDC42	ENST00000539522.2	c.232G>C	p.Glu78Gln	missense_variant	3/6	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.232G>C (p.E78Q) alteration is located in exon 3 (coding exon 3) of the CCDC42 gene. This alteration results from a G to C substitution at nucleotide position 232, causing the glutamic acid (E) at amino acid position 78 to be replaced by a glutamine (Q). 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	0.14
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0081	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.49	T;T
Polyphen		0.99	D;.
Vest4		0.34
MutPred		0.26		Gain of MoRF binding (P = 0.0309);Gain of MoRF binding (P = 0.0309);
MVP		0.32
MPC		1.0
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.73
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8647006;