Variant 17-8735181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144681.3(CCDC42):c.788C>T(p.Thr263Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,140 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 6 hom. )

Consequence

CCDC42
NM_144681.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14128348).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC42	NM_144681.3 linkuse as main transcript	c.788C>T	p.Thr263Met	missense_variant	6/7	ENST00000293845.8	NP_653282.2
CCDC42	NM_001158261.2 linkuse as main transcript	c.566C>T	p.Thr189Met	missense_variant	5/6		NP_001151733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC42	ENST00000293845.8 linkuse as main transcript	c.788C>T	p.Thr263Met	missense_variant	6/7	2	NM_144681.3	ENSP00000293845	P1	Q96M95-1
CCDC42	ENST00000539522.2 linkuse as main transcript	c.566C>T	p.Thr189Met	missense_variant	5/6	1		ENSP00000444359		Q96M95-2

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000879

AC:

221

AN:

251418

Hom.:

AF XY:

0.000942

AC XY:

128

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00154

AC:

2246

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1068

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152256

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.788C>T (p.T263M) alteration is located in exon 6 (coding exon 6) of the CCDC42 gene. This alteration results from a C to T substitution at nucleotide position 788, causing the threonine (T) at amino acid position 263 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

1.0

D;.

Vest4

0.77

MVP

0.37

MPC

0.96

ClinPred

0.040

GERP RS

5.1

Varity_R

0.13

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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