rs186738044

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001378030.1(CCDC78):c.781G>A(p.Ala261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000976 in 1,599,162 control chromosomes in the GnomAD database, including 17 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. A261G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 15 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

Publications

0 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: Orphanet, G2P, 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031004548).

BP6

Variant 16-724494-C-T is Benign according to our data. Variant chr16-724494-C-T is described in ClinVar as Benign. ClinVar VariationId is 540479.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 376 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378030.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC78	NM_001378030.1	MANE Select	c.781G>A	p.Ala261Thr	missense	Exon 9 of 14	NP_001364959.1	H3BLT8
CCDC78	NM_001031737.3		c.781G>A	p.Ala261Thr	missense	Exon 9 of 14	NP_001026907.2	A2IDD5-1
CCDC78	NM_001378031.1		c.781G>A	p.Ala261Thr	missense	Exon 9 of 12	NP_001364960.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.781G>A	p.Ala261Thr	missense	Exon 9 of 14	ENSP00000316851.5	H3BLT8
CCDC78	ENST00000293889.10	TSL:1	c.781G>A	p.Ala261Thr	missense	Exon 9 of 14	ENSP00000293889.6	A2IDD5-1
CCDC78	ENST00000947033.1		c.781G>A	p.Ala261Thr	missense	Exon 9 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0307

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00163

AC:

371

AN:

227892

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.0254

Gnomad NFE exome

AF:

0.000346

Gnomad OTH exome

AF:

0.00226

GnomAD4 exome

AF:

0.000819

AC:

1185

AN:

1446818

Hom.:

Cov.:

AF XY:

0.000823

AC XY:

593

AN XY:

720206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.000101

AC:

AN:

39662

South Asian (SAS)

AF:

0.000139

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.0245

AC:

966

AN:

39458

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000140

AC:

156

AN:

1111390

Other (OTH)

AF:

0.000747

AC:

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

169

253

338

422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00247

AC:

376

AN:

152344

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0307

AC:

326

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68032

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000614

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00181

AC:

217

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital myopathy with internal nuclei and atypical cores (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.52

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.38

PhyloP100

-1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.65

REVEL

Benign

0.030

Sift

Benign

0.57

Sift4G

Benign

0.56

Polyphen

0.071

Vest4

0.10

MVP

0.048

MPC

0.071

ClinPred

0.014

GERP RS

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.034

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over