Variant rs61998220 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001378030.1(CCDC78):c.889C>T(p.Arg297Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000852 in 1,611,818 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R297H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0043 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 6 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.17

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00530532).

BP6

Variant 16-724386-G-A is Benign according to our data. Variant chr16-724386-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 473269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 650 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1 linkuse as main transcript	c.889C>T	p.Arg297Cys	missense_variant	9/14	ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10 linkuse as main transcript	c.889C>T	p.Arg297Cys	missense_variant	9/14	5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00136

AC:

335

AN:

246486

Hom.:

AF XY:

0.00109

AC XY:

146

AN XY:

134076

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00313

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000495

AC:

723

AN:

1459510

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

297

AN XY:

726092

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.000940

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00427

AC:

650

AN:

152308

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00504

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00157

AC:

190

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 10, 2020

- -

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

0.16

Eigen_PC

Benign

0.0055

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.1

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.47

MVP

0.27

MPC

0.44

ClinPred

0.029

GERP RS

3.9

Varity_R

0.32

gMVP

0.29

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