chr17-8735406-C-T

Variant names:

• chr17-8735406-C-T
• NM_144681.3:c.698G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144681.3(CCDC42):​c.698G>A​(p.Ser233Asn) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC42 NM_144681.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

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

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=0.24714234).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144681.3. 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
	CCDC42	NM_144681.3	MANE Select	c.698G>A	p.Ser233Asn	missense	Exon 5 of 7	NP_653282.2	Q96M95-1
	CCDC42	NM_001158261.2		c.493-152G>A		intron	N/A	NP_001151733.1	Q96M95-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC42	ENST00000293845.8	TSL:2 MANE Select	c.698G>A	p.Ser233Asn	missense	Exon 5 of 7	ENSP00000293845.3	Q96M95-1
	CCDC42	ENST00000539522.2	TSL:1	c.493-152G>A		intron	N/A	ENSP00000444359.2	Q96M95-2
	CCDC42	ENST00000857513.1		c.698G>A	p.Ser233Asn	missense	Exon 6 of 8	ENSP00000527572.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.054
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Polyphen		0.47	P
Vest4		0.51
MutPred		0.31		Loss of phosphorylation at S233 (P = 0.0561)
MVP		0.40
MPC		0.98
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.86

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

Other links and lift over

hg19: chr17-8638724;