rs61998209

chr16-724338-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378030.1(CCDC78):c.937C>T(p.Leu313=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00332 in 1,611,772 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (88 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (74 hom.)
• Consequence: CCDC78 NM_001378030.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.08

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-724338-G-A is Benign according to our data. Variant chr16-724338-G-A is described in ClinVar as [Benign]. Clinvar id is 128633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1	c.937C>T	p.Leu313=	synonymous_variant	9/14	ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10	c.937C>T	p.Leu313=	synonymous_variant	9/14	5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2632 AN: 152160 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00478 AC: 1191 AN: 249224 Hom.: 34 AF XY: 0.00332 AC XY: 448 AN XY: 135098

Gnomad AFR exome AF: 0.0631

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00211

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00185 AC: 2707 AN: 1459494 Hom.: 74 Cov.: 35 AF XY: 0.00156 AC XY: 1133 AN XY: 725854

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000729

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.0173 AC: 2640 AN: 152278 Hom.: 88 Cov.: 33 AF XY: 0.0165 AC XY: 1227 AN XY: 74452

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00875 Hom.: 13

Bravo AF: 0.0206

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Congenital myopathy with internal nuclei and atypical cores Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	2.5
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs61998209; hg19: chr16-774338;