Variant 16-724193-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001378030.1(CCDC78):c.966C>A(p.Asn322Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,597,364 control chromosomes in the GnomAD database, including 43 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 42 hom. )

Consequence

CCDC78
NM_001378030.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.909

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003260076).

BP6

Variant 16-724193-G-T is Benign according to our data. Variant chr16-724193-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 128634.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}. Variant chr16-724193-G-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1 linkuse as main transcript	c.966C>A	p.Asn322Lys	missense_variant	10/14	ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10 linkuse as main transcript	c.966C>A	p.Asn322Lys	missense_variant	10/14	5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00376

AC:

885

AN:

235528

Hom.:

AF XY:

0.00456

AC XY:

581

AN XY:

127412

show subpopulations

Gnomad AFR exome

AF:

0.000878

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.000233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.000481

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00407

AC:

5880

AN:

1445038

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

3156

AN XY:

717322

show subpopulations

Gnomad4 AFR exome

AF:

0.000574

Gnomad4 AMR exome

AF:

0.000628

Gnomad4 ASJ exome

AF:

0.0000800

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00391

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152326

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00362

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00206

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00371

AC:

450

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 24, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.3

DANN

Benign

0.55

DEOGEN2

Benign

0.015

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.63

REVEL

Benign

0.021

Sift

Benign

0.47

Sift4G

Uncertain

0.037

Polyphen

0.027

Vest4

0.060

MutPred

0.35

Gain of methylation at N322 (P = 0.009);

MVP

0.11

MPC

0.21

ClinPred

0.00010

GERP RS

1.8

Varity_R

0.047

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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