rs148276717

Variant names:

• chr16-722985-C-T
• rs148276717
• NM_001378030.1:c.1238G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-722985-C-T
• chr16-722985-C-A
• chr16-722985-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_001378030.1(CCDC78):​c.1238G>A​(p.Arg413Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,612,442 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CCDC78 NM_001378030.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.10
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0136344135).
• BP6: Variant 16-722985-C-T is Benign according to our data. Variant chr16-722985-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 447007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 242 AD gene.

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.1238G>A	p.Arg413Gln	missense	Exon 13 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.1234G>A	p.Gly412Arg	missense	Exon 13 of 14	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.1058G>A	p.Arg353Gln	missense	Exon 11 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.1238G>A	p.Arg413Gln	missense	Exon 13 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.1234G>A	p.Gly412Arg	missense	Exon 13 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.1238G>A	p.Arg413Gln	missense	Exon 13 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152218 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000385 AC: 96 AN: 249502 AF XY: 0.000288

Gnomad AFR exome AF: 0.00547

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000163 AC: 238 AN: 1460106 Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 97 AN XY: 726366

African (AFR) AF: 0.00579 AC: 194 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44716

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51708

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

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111968

Other (OTH) AF: 0.000265 AC: 16 AN: 60372

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152336 Hom.: 1 Cov.: 34 AF XY: 0.00142 AC XY: 106 AN XY: 74488

African (AFR) AF: 0.00532 AC: 221 AN: 41572

American (AMR) AF: 0.000915 AC: 14 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000571 Hom.: 0

Bravo AF: 0.00183

ESP6500AA AF: 0.00410 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000479 AC: 58

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0079	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.36		Gain of helix (P = 0.062)
MVP		0.41
MPC		0.42
ClinPred		0.059	T
GERP RS		4.5
Varity_R		0.17
gMVP		0.088
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs148276717; hg19: chr16-772985;