Variant chr16-722978-C-T 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_001031737.3(CCDC78):c.1241G>A(p.Arg414Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,612,446 control chromosomes in the GnomAD database, including 3 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 0.00087 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00028 ( 3 hom. )

Consequence

CCDC78
NM_001031737.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.94

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:

CCDC78 (HGNC:):

CCDC78 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005996585).

BP6

Variant 16-722978-C-T is Benign according to our data. Variant chr16-722978-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-722978-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC78	NM_001378030.1 linkuse as main transcript	c.1245G>A	p.Thr415Thr	synonymous_variant	13/14	ENST00000345165.10	NP_001364959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC78	ENST00000345165.10 linkuse as main transcript	c.1245G>A	p.Thr415Thr	synonymous_variant	13/14	5	NM_001378030.1	ENSP00000316851.5		H3BLT8

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

131

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000617

AC:

154

AN:

249520

Hom.:

AF XY:

0.000664

AC XY:

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000279

AC:

407

AN:

1460096

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

262

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00247

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152350

Hom.:

Cov.:

AF XY:

0.000899

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000320

Hom.:

Bravo

AF:

0.00102

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000561

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

CCDC78-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 01, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.17

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.49

M_CAP

Benign

0.0080

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.98

REVEL

Benign

0.17

Sift

Benign

0.092

Sift4G

Uncertain

0.025

Polyphen

0.11

Vest4

0.17

MVP

0.081

MPC

0.17

ClinPred

0.0098

GERP RS

-7.5

Varity_R

0.023

gMVP

0.047

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

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