rs8055909

Variant names:

• chr16-725089-C-T
• rs8055909
• NM_001378030.1:c.549G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378033.1(CCDC78):​c.187G>A​(p.Gly63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,612,740 control chromosomes in the GnomAD database, including 564 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (276 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (288 hom.)
• Consequence: CCDC78 NM_001378033.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.391
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital myopathy with internal nuclei and atypical cores

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• centronuclear myopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-725089-C-T is Benign according to our data. Variant chr16-725089-C-T is described in ClinVar as Benign. ClinVar VariationId is 128629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378033.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	NM_001378030.1	MANE Select	c.549G>A	p.Leu183Leu	synonymous	Exon 6 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001378033.1		c.187G>A	p.Gly63Ser	missense	Exon 4 of 10	NP_001364962.1
	CCDC78	NM_001031737.3		c.549G>A	p.Leu183Leu	synonymous	Exon 6 of 14	NP_001026907.2	A2IDD5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.549G>A	p.Leu183Leu	synonymous	Exon 6 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.549G>A	p.Leu183Leu	synonymous	Exon 6 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.549G>A	p.Leu183Leu	synonymous	Exon 6 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4990 AN: 152216 Hom.: 274 Cov.: 34

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00883 AC: 2204 AN: 249666 AF XY: 0.00654

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000392

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00344 AC: 5026 AN: 1460406 Hom.: 288 Cov.: 37 AF XY: 0.00306 AC XY: 2221 AN XY: 726478

African (AFR) AF: 0.121 AC: 4041 AN: 33480

American (AMR) AF: 0.00532 AC: 238 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52072

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000174 AC: 194 AN: 1111910

Other (OTH) AF: 0.00818 AC: 494 AN: 60362

GnomAD4 genome AF: 0.0328 AC: 4997 AN: 152334 Hom.: 276 Cov.: 34 AF XY: 0.0312 AC XY: 2323 AN XY: 74486

African (AFR) AF: 0.115 AC: 4776 AN: 41552

American (AMR) AF: 0.00973 AC: 149 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68034

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0312 Hom.: 197

Bravo AF: 0.0373

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Congenital myopathy with internal nuclei and atypical cores (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.76
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8055909; hg19: chr16-775089;