16-722645-AGCTCT-AGCTCTGCTCT

Variant names:

• chr16-722645-A-AGCTCT
• rs553588726
• NM_001378030.1:c.*28_*32dupAGAGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001378030.1(CCDC78):​c.*28_*32dupAGAGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,595,102 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: CCDC78 NM_001378030.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• 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]

ANTKMT (HGNC:14152): (adenine nucleotide translocase lysine methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 485 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.*28_*32dupAGAGC		3_prime_UTR	Exon 14 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.*120_*124dupAGAGC		3_prime_UTR	Exon 14 of 14	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.*28_*32dupAGAGC		3_prime_UTR	Exon 12 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.*28_*32dupAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.*120_*124dupAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.*28_*32dupAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000617092.1

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 486 AN: 151912 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00955

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00339 AC: 806 AN: 238024 AF XY: 0.00358

Gnomad AFR exome AF: 0.000456

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00215

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00948

Gnomad NFE exome AF: 0.00416

Gnomad OTH exome AF: 0.00355

GnomAD4 exome AF: 0.00342 AC: 4937 AN: 1443072 Hom.: 13 Cov.: 34 AF XY: 0.00342 AC XY: 2455 AN XY: 717278

African (AFR) AF: 0.000391 AC: 13 AN: 33230

American (AMR) AF: 0.00186 AC: 83 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 62 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00355 AC: 305 AN: 85990

European-Finnish (FIN) AF: 0.0101 AC: 420 AN: 41622

Middle Eastern (MID) AF: 0.00575 AC: 33 AN: 5738

European-Non Finnish (NFE) AF: 0.00344 AC: 3808 AN: 1106484

Other (OTH) AF: 0.00355 AC: 213 AN: 59984

GnomAD4 genome AF: 0.00319 AC: 485 AN: 152030 Hom.: 0 Cov.: 33 AF XY: 0.00335 AC XY: 249 AN XY: 74314

African (AFR) AF: 0.000483 AC: 20 AN: 41420

American (AMR) AF: 0.00288 AC: 44 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.00955 AC: 101 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00410 AC: 279 AN: 67966

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00202 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs553588726; hg19: chr16-772645;