16-722645-A-AGCTCTGCTCT

Variant names:

• chr16-722645-A-AGCTCTGCTCT
• rs553588726
• NM_001378030.1:c.*23_*32dupAGAGCAGAGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001378030.1(CCDC78):​c.*23_*32dupAGAGCAGAGC 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
• 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1390 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.*23_*32dupAGAGCAGAGC		3_prime_UTR	Exon 14 of 14	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.*115_*124dupAGAGCAGAGC		3_prime_UTR	Exon 14 of 14	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.*23_*32dupAGAGCAGAGC		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.*23_*32dupAGAGCAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.*115_*124dupAGAGCAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.*23_*32dupAGAGCAGAGC		3_prime_UTR	Exon 14 of 14	ENSP00000617092.1

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

GnomAD2 exomes AF: 0.00229 AC: 545 AN: 238024 AF XY: 0.00163

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 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

African (AFR) AF: 0.0340 AC: 1128 AN: 33216

American (AMR) AF: 0.00193 AC: 86 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

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

South Asian (SAS) AF: 0.000186 AC: 16 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41626

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5738

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1106538

Other (OTH) AF: 0.00212 AC: 127 AN: 59982

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

African (AFR) AF: 0.0316 AC: 1310 AN: 41398

American (AMR) AF: 0.00373 AC: 57 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67970

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.000331 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;