chr16-725432-G-A

Variant names:

• chr16-725432-G-A
• rs374382609
• NM_001378030.1:c.416C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378030.1(CCDC78):​c.416C>T​(p.Ser139Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CCDC78 NM_001378030.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12721229).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378030.1. 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.416C>T	p.Ser139Phe	missense	Exon 4 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.416C>T	p.Ser139Phe	missense	Exon 4 of 14	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.416C>T	p.Ser139Phe	missense	Exon 4 of 12	NP_001364960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.416C>T	p.Ser139Phe	missense	Exon 4 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.416C>T	p.Ser139Phe	missense	Exon 4 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.416C>T	p.Ser139Phe	missense	Exon 4 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital myopathy with internal nuclei and atypical cores (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.038
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.068	T
Sift4G	Uncertain	0.052	T
Polyphen		0.93	P
Vest4		0.34
MutPred		0.26		Loss of sheet (P = 0.1158)
MVP		0.23
MPC		0.16
ClinPred		0.17	T
GERP RS		0.53
Varity_R		0.058
gMVP		0.059

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs374382609; hg19: chr16-775432;