rs146067716

Variant names:

• chr16-722978-C-T
• rs146067716
• ENST00000293889.10:c.1241G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-722978-C-T
• chr16-722978-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001031737.3(CCDC78):​c.1241G>A​(p.Arg414Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,612,446 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (3 hom.)
• Consequence: CCDC78 NM_001031737.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.94
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005996585).
• BP6: Variant 16-722978-C-T is Benign according to our data. Variant chr16-722978-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 473251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 133 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031737.3. 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.1245G>A	p.Thr415Thr	synonymous	Exon 13 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.1241G>A	p.Arg414Gln	missense	Exon 13 of 14	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.1065G>A	p.Thr355Thr	synonymous	Exon 11 of 12	NP_001364960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	ENST00000293889.10	TSL:1	c.1241G>A	p.Arg414Gln	missense	Exon 13 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.1245G>A	p.Thr415Thr	synonymous	Exon 13 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000947033.1		c.1245G>A	p.Thr415Thr	synonymous	Exon 13 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152232 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000617 AC: 154 AN: 249520 AF XY: 0.000664

Gnomad AFR exome AF: 0.00199

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000279 AC: 407 AN: 1460096 Hom.: 3 Cov.: 34 AF XY: 0.000361 AC XY: 262 AN XY: 726368

African (AFR) AF: 0.00233 AC: 78 AN: 33480

American (AMR) AF: 0.000895 AC: 40 AN: 44716

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

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39700

South Asian (SAS) AF: 0.00247 AC: 213 AN: 86258

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111972

Other (OTH) AF: 0.000878 AC: 53 AN: 60376

GnomAD4 genome AF: 0.000873 AC: 133 AN: 152350 Hom.: 0 Cov.: 34 AF XY: 0.000899 AC XY: 67 AN XY: 74492

African (AFR) AF: 0.00238 AC: 99 AN: 41582

American (AMR) AF: 0.000588 AC: 9 AN: 15308

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

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000399 Hom.: 2

Bravo AF: 0.00102

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000561 AC: 68

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CCDC78-related disorder (1)
-	-	1	Congenital myopathy with internal nuclei and atypical cores (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-3.9
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.17
Sift	Benign	0.092	T
Sift4G	Uncertain	0.025	D
Polyphen		0.11	B
Vest4		0.17
MVP		0.081
MPC		0.17
ClinPred		0.0098	T
GERP RS		-7.5
Varity_R		0.023
gMVP		0.047
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs146067716; hg19: chr16-772978;