16-722797-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001378030.1(CCDC78):c.1302-8C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000879 in 1,612,552 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: CCDC78 NM_001378030.1 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.6615
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.381

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-722797-G-T is Benign according to our data. Variant chr16-722797-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 473253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1	c.1302-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10	c.1302-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152196 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000485 AC: 121 AN: 249556 Hom.: 0 AF XY: 0.000450 AC XY: 61 AN XY: 135498

Gnomad AFR exome AF: 0.000372

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000926

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000912 AC: 1332 AN: 1460238 Hom.: 1 Cov.: 34 AF XY: 0.000852 AC XY: 619 AN XY: 726420

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152314 Hom.: 0 Cov.: 34 AF XY: 0.000443 AC XY: 33 AN XY: 74472

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000778 Hom.: 0

Bravo AF: 0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CCDC78: BP4 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 10, 2020	- -

Congenital myopathy with internal nuclei and atypical cores Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.1
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.66
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.070		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: rs201006875; hg19: chr16-772797;