18-54937957-C-T

Position:

• chr18-54937957-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_025214.3(CCDC68):​c.345G>A​(p.Lys115Lys) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.218 in 1,606,080 control chromosomes in the GnomAD database, including 40,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2853 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37983 hom.)
• Consequence: CCDC68 NM_025214.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05

Genes affected

CCDC68 (HGNC:24350): (coiled-coil domain containing 68) Involved in microtubule anchoring at centrosome and protein localization. Located in centriole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

CCDC68 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC68	NM_025214.3	c.345G>A	p.Lys115Lys	splice_region_variant, synonymous_variant	5/12	ENST00000591504.6	NP_079490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC68	ENST00000591504.6	c.345G>A	p.Lys115Lys	splice_region_variant, synonymous_variant	5/12	1	NM_025214.3	ENSP00000466690.1
CCDC68	ENST00000432185.5	c.345G>A	p.Lys115Lys	splice_region_variant, synonymous_variant	3/10	1		ENSP00000413406.1
CCDC68	ENST00000337363.8	c.345G>A	p.Lys115Lys	splice_region_variant, synonymous_variant	5/12	2		ENSP00000337209.3
CCDC68	ENST00000587148.2	n.726G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26503 AN: 152044 Hom.: 2854 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.202 AC: 49560 AN: 245240 Hom.: 5680 AF XY: 0.207 AC XY: 27474 AN XY: 132500

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.307

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.223 AC: 323670 AN: 1453918 Hom.: 37983 Cov.: 31 AF XY: 0.224 AC XY: 161635 AN XY: 723026

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.174 AC: 26501 AN: 152162 Hom.: 2853 Cov.: 33 AF XY: 0.174 AC XY: 12926 AN XY: 74390

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.207

Alfa AF: 0.226 Hom.: 7621

Bravo AF: 0.162

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1344011; hg19: chr18-52605188; COSMIC: COSV61603800; COSMIC: COSV61603800;