Variant 17-8735559-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144681.3(CCDC42):c.545G>A(p.Arg182His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,778 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

CCDC42
NM_144681.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.36

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05567509).

BP6

Variant 17-8735559-C-T is Benign according to our data. Variant chr17-8735559-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3264214.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC42	NM_144681.3 linkuse as main transcript	c.545G>A	p.Arg182His	missense_variant	5/7	ENST00000293845.8	NP_653282.2
CCDC42	NM_001158261.2 linkuse as main transcript	c.493-305G>A		intron_variant			NP_001151733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC42	ENST00000293845.8 linkuse as main transcript	c.545G>A	p.Arg182His	missense_variant	5/7	2	NM_144681.3	ENSP00000293845	P1	Q96M95-1
CCDC42	ENST00000539522.2 linkuse as main transcript	c.493-305G>A		intron_variant		1		ENSP00000444359		Q96M95-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251068

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.41

M_CAP

Benign

0.0038

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.7

REVEL

Benign

0.030

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.26

MVP

0.17

MPC

0.38

ClinPred

0.055

GERP RS

3.2

Varity_R

0.030

gMVP

0.53

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.

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