Variant 19-46411290-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032040.5(CCDC8):c.1521G>C(p.Lys507Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,614,146 control chromosomes in the GnomAD database, including 3,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.056 ( 296 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2870 hom. )

Consequence

CCDC8
NM_032040.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

CCDC8 (HGNC:25367): (coiled-coil domain containing 8) This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a cofactor required for p53-mediated apoptosis following DNA damage, and may also play a role in growth through interactions with the cytoskeletal adaptor protein obscurin-like 1. Mutations in this gene are a cause of 3M syndrome-3 (3M3). [provided by RefSeq, Dec 2011]

CCDC8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014494061).

BP6

Variant 19-46411290-C-G is Benign according to our data. Variant chr19-46411290-C-G is described in ClinVar as [Benign]. Clinvar id is 262004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-46411290-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC8	NM_032040.5 linkuse as main transcript	c.1521G>C	p.Lys507Asn	missense_variant	1/1	ENST00000307522.5	NP_114429.2	Q9H0W5G8IFA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC8	ENST00000307522.5 linkuse as main transcript	c.1521G>C	p.Lys507Asn	missense_variant	1/1	6	NM_032040.5	ENSP00000303158.3		Q9H0W5
CCDC8	ENST00000697726.1 linkuse as main transcript	c.1731G>C	p.Lys577Asn	missense_variant	1/1			ENSP00000513420.1		A0A8V8TMN3

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8522

AN:

152148

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0521

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0494

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0726

AC:

18247

AN:

251422

Hom.:

967

AF XY:

0.0710

AC XY:

9643

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.0970

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.0735

Gnomad FIN exome

AF:

0.0995

Gnomad NFE exome

AF:

0.0498

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0558

AC:

81559

AN:

1461880

Hom.:

2870

Cov.:

AF XY:

0.0561

AC XY:

40765

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.0900

Gnomad4 ASJ exome

AF:

0.0317

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.0717

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0487

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.0560

AC:

8526

AN:

152266

Hom.:

296

Cov.:

AF XY:

0.0587

AC XY:

4369

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.0522

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.0810

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.0494

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0519

Hom.:

225

Bravo

AF:

0.0534

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0496

AC:

191

ESP6500AA

AF:

0.0381

AC:

168

ESP6500EA

AF:

0.0474

AC:

408

ExAC

AF:

0.0707

AC:

8585

Asia WGS

AF:

0.132

AC:

459

AN:

3478

EpiCase

AF:

0.0454

EpiControl

AF:

0.0446

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0041

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.10

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.050

.;T

Polyphen

0.90

P;P

Vest4

0.088

MutPred

0.076

Loss of methylation at K507 (P = 0.0061);Loss of methylation at K507 (P = 0.0061);

MPC

0.87

ClinPred

0.022

GERP RS

4.0

Varity_R

0.55

gMVP

0.15

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