16-724692-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378030.1(CCDC78):c.754T>C(p.Trp252Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,609,756 control chromosomes in the GnomAD database, including 233,436 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W252Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.57 ( 26003 hom., cov: 34)

Exomes 𝑓: 0.52 ( 207433 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.155

Publications

43 publications found

Variant links:

Genes affected

CCDC78 (HGNC:14153): (coiled-coil domain containing 78) Involved in de novo centriole assembly involved in multi-ciliated epithelial cell differentiation and skeletal muscle contraction. Located in several cellular components, including centriole; deuterosome; and sarcolemma. Implicated in centronuclear myopathy 4. [provided by Alliance of Genome Resources, Apr 2022]

CCDC78 Gene-Disease associations (from GenCC):

congenital myopathy with internal nuclei and atypical cores
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
centronuclear myopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CCDC78 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.842575E-7).

BP6

Variant 16-724692-A-G is Benign according to our data. Variant chr16-724692-A-G is described in ClinVar as Benign. ClinVar VariationId is 128631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC78	NM_001378030.1 link	c.754T>C	p.Trp252Arg	missense_variant	Exon 8 of 14	ENST00000345165.10	NP_001364959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC78	ENST00000345165.10 link	c.754T>C	p.Trp252Arg	missense_variant	Exon 8 of 14	5	NM_001378030.1	ENSP00000316851.5

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87034

AN:

151994

Hom.:

25963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.812

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.501

GnomAD2 exomes

AF:

0.599

AC:

146181

AN:

243926

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.729

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.844

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.522

AC:

760220

AN:

1457644

Hom.:

207433

Cov.:

AF XY:

0.528

AC XY:

382649

AN XY:

725156

show subpopulations

African (AFR)

AF:

0.669

AC:

22380

AN:

33466

American (AMR)

AF:

0.713

AC:

31697

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

10545

AN:

26102

East Asian (EAS)

AF:

0.822

AC:

32595

AN:

39662

South Asian (SAS)

AF:

0.797

AC:

68578

AN:

86036

European-Finnish (FIN)

AF:

0.606

AC:

30719

AN:

50674

Middle Eastern (MID)

AF:

0.383

AC:

2209

AN:

5764

European-Non Finnish (NFE)

AF:

0.477

AC:

529784

AN:

1111230

Other (OTH)

AF:

0.527

AC:

31713

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

22329

44657

66986

89314

111643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15928

31856

47784

63712

79640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.573

AC:

87132

AN:

152112

Hom.:

26003

Cov.:

AF XY:

0.585

AC XY:

43537

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.664

AC:

27559

AN:

41484

American (AMR)

AF:

0.607

AC:

9290

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1405

AN:

3470

East Asian (EAS)

AF:

0.833

AC:

4308

AN:

5170

South Asian (SAS)

AF:

0.813

AC:

3922

AN:

4826

European-Finnish (FIN)

AF:

0.604

AC:

6406

AN:

10604

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.480

AC:

32632

AN:

67950

Other (OTH)

AF:

0.505

AC:

1064

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1897

3794

5692

7589

9486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.492

Hom.:

33771

Bravo

AF:

0.572

TwinsUK

AF:

0.482

AC:

1788

ALSPAC

AF:

0.470

AC:

1810

ESP6500AA

AF:

0.661

AC:

2889

ESP6500EA

AF:

0.472

AC:

4046

ExAC

AF:

0.593

AC:

71350

Asia WGS

AF:

0.803

AC:

2789

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital myopathy with internal nuclei and atypical cores

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.85

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.0044

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.14

MetaRNN

Benign

8.8e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.1

PhyloP100

-0.15

PrimateAI

Benign

0.28

PROVEAN

Benign

3.5

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.017

ClinPred

0.0036

GERP RS

1.8

Varity_R

0.034

gMVP

0.040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over