16-722645-A-AGCTCTGCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001378030.1(CCDC78):c.*32_*33insAGAGCAGAGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,595,132 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (24 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (29 hom.)
• Consequence: CCDC78 NM_001378030.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171

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 -10 ACMG points.

• BP6: Variant 16-722645-A-AGCTCTGCTCT is Benign according to our data. Variant chr16-722645-A-AGCTCTGCTCT is described in ClinVar as [Likely_benign]. Clinvar id is 1316891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00914 (1390/152012) while in subpopulation AFR AF= 0.0316 (1310/41398). AF 95% confidence interval is 0.0302. There are 24 homozygotes in gnomad4. There are 636 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1380 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1	c.*32_*33insAGAGCAGAGC		3_prime_UTR_variant	14/14	ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10	c.*32_*33insAGAGCAGAGC		3_prime_UTR_variant	14/14	5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes AF: 0.00909 AC: 1380 AN: 151894 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00229 AC: 545 AN: 238024 Hom.: 12 AF XY: 0.00163 AC XY: 212 AN XY: 130394

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000364

Gnomad OTH exome AF: 0.000675

GnomAD4 exome AF: 0.000961 AC: 1387 AN: 1443120 Hom.: 29 Cov.: 34 AF XY: 0.000782 AC XY: 561 AN XY: 717298

Gnomad4 AFR exome AF: 0.0340

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000145

Gnomad4 OTH exome AF: 0.00212

GnomAD4 genome AF: 0.00914 AC: 1390 AN: 152012 Hom.: 24 Cov.: 33 AF XY: 0.00856 AC XY: 636 AN XY: 74302

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00805

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 19, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs553588726; hg19: chr16-772645;