rs142136104

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001378030.1(CCDC78):c.712A>C(p.Lys238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,612,256 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 9 hom., cov: 34)

Exomes 𝑓: 0.011 ( 111 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0300

Publications

8 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00590384).

BP6

Variant 16-724734-T-G is Benign according to our data. Variant chr16-724734-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1242 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.712A>C	p.Lys238Gln	missense	Exon 8 of 14	NP_001364959.1	H3BLT8
CCDC78	NM_001031737.3		c.712A>C	p.Lys238Gln	missense	Exon 8 of 14	NP_001026907.2	A2IDD5-1
CCDC78	NM_001378031.1		c.712A>C	p.Lys238Gln	missense	Exon 8 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.712A>C	p.Lys238Gln	missense	Exon 8 of 14	ENSP00000316851.5	H3BLT8
CCDC78	ENST00000293889.10	TSL:1	c.712A>C	p.Lys238Gln	missense	Exon 8 of 14	ENSP00000293889.6	A2IDD5-1
CCDC78	ENST00000947033.1		c.712A>C	p.Lys238Gln	missense	Exon 8 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes

AF:

0.00816

AC:

1242

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00912

AC:

2257

AN:

247470

AF XY:

0.00926

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00503

Gnomad EAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00845

GnomAD4 exome

AF:

0.0114

AC:

16699

AN:

1459948

Hom.:

111

Cov.:

AF XY:

0.0113

AC XY:

8208

AN XY:

726232

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

33472

American (AMR)

AF:

0.00253

AC:

113

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00536

AC:

140

AN:

26120

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39692

South Asian (SAS)

AF:

0.00636

AC:

548

AN:

86144

European-Finnish (FIN)

AF:

0.0185

AC:

961

AN:

51944

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0128

AC:

14286

AN:

1111806

Other (OTH)

AF:

0.00918

AC:

554

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1050

2100

3149

4199

5249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.00815

AC:

1242

AN:

152308

Hom.:

Cov.:

AF XY:

0.00833

AC XY:

620

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

41558

American (AMR)

AF:

0.00248

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00435

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0203

AC:

216

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

823

AN:

68024

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0100

Hom.:

Bravo

AF:

0.00679

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00206

AC:

ESP6500EA

AF:

0.0124

AC:

106

ExAC

AF:

0.00941

AC:

1134

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0108

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Congenital myopathy with internal nuclei and atypical cores (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.030

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

REVEL

Benign

0.037

Sift

Benign

0.089

Sift4G

Uncertain

0.017

Polyphen

0.93

Vest4

0.27

MVP

0.13

MPC

0.23

ClinPred

0.011

GERP RS

3.1

Varity_R

0.075

gMVP

0.049

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over