Variant 17-8741496-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144681.3(CCDC42):c.470A>G(p.Glu157Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CCDC42
NM_144681.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC42	NM_144681.3 linkuse as main transcript	c.470A>G	p.Glu157Gly	missense_variant	4/7	ENST00000293845.8
CCDC42	NM_001158261.2 linkuse as main transcript	c.470A>G	p.Glu157Gly	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC42	ENST00000293845.8 linkuse as main transcript	c.470A>G	p.Glu157Gly	missense_variant	4/7	2	NM_144681.3	P1	Q96M95-1
CCDC42	ENST00000539522.2 linkuse as main transcript	c.470A>G	p.Glu157Gly	missense_variant	4/6	1			Q96M95-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000758

AC:

AN:

250592

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000492

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000277

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000988

AC:

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

Aug 23, 2021

The c.470A>G (p.E157G) alteration is located in exon 4 (coding exon 4) of the CCDC42 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the glutamic acid (E) at amino acid position 157 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;T

Sift4G

Benign

0.17

T;D

Polyphen

1.0

D;.

Vest4

0.68

MutPred

0.68

Loss of stability (P = 0.0189);Loss of stability (P = 0.0189);

MVP

0.40

MPC

0.65

ClinPred

0.42

GERP RS

4.3

Varity_R

0.73

gMVP

0.57

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