NM_001378030.1:c.803C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378030.1(CCDC78):c.803C>T(p.Thr268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000897 in 1,601,088 control chromosomes in the GnomAD database, including 12 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 7 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.740

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=0.004002303).

BP6

Variant 16-724472-G-A is Benign according to our data. Variant chr16-724472-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 128632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00469 (715/152330) while in subpopulation AFR AF= 0.0162 (673/41572). AF 95% confidence interval is 0.0152. There are 5 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 715 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC78	NM_001378030.1 link	c.803C>T	p.Thr268Met	missense_variant	Exon 9 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.803C>T	p.Thr268Met	missense_variant	Exon 9 of 14	5	NM_001378030.1	ENSP00000316851.5		H3BLT8

Frequencies

GnomAD3 genomes

AF:

0.00469

AC:

714

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00135

AC:

313

AN:

231626

Hom.:

AF XY:

0.000961

AC XY:

123

AN XY:

128014

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000568

Gnomad OTH exome

AF:

0.000686

GnomAD4 exome

AF:

0.000498

AC:

721

AN:

1448758

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

310

AN XY:

721200

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000945

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00469

AC:

715

AN:

152330

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

342

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000733

Hom.:

Bravo

AF:

0.00490

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00153

AC:

184

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 16, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.1

DANN

Benign

0.94

DEOGEN2

Benign

0.025

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

REVEL

Benign

0.015

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.22

Vest4

0.11

MVP

0.040

MPC

0.064

ClinPred

0.00065

GERP RS

-2.3

Varity_R

0.014

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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