16-724692-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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 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=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 id is 128631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-724692-A-G is described in Lovd as [Benign].

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		H3BLT8

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

GnomAD3 exomes

AF:

0.599

AC:

146181

AN:

243926

Hom.:

46610

AF XY:

0.596

AC XY:

79336

AN XY:

133106

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 SAS exome

AF:

0.807

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

Gnomad4 AFR exome

AF:

0.669

Gnomad4 AMR exome

AF:

0.713

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.797

Gnomad4 FIN exome

AF:

0.606

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.527

GnomAD4 genome

AF:

0.573

AC:

87132

AN:

152112

Hom.:

26003

Cov.:

AF XY:

0.585

AC XY:

43537

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.405

Gnomad4 EAS

AF:

0.833

Gnomad4 SAS

AF:

0.813

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.480

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.478

Hom.:

20969

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

- -

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

- -

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

- -

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

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

PrimateAI

Benign

0.28

PROVEAN

Benign

3.5

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MutPred

0.20

Gain of disorder (P = 0.0032);

MPC

0.11

ClinPred

0.0036

GERP RS

1.8

Varity_R

0.034

gMVP

0.040

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