18-54937957-C-T

Variant names:

• chr18-54937957-C-T
• rs1344011
• NM_025214.3:c.345G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 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
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC68	NM_025214.3	MANE Select	c.345G>A	p.Lys115Lys	splice_region synonymous	Exon 5 of 12	NP_079490.1
	CCDC68	NM_001143829.2		c.345G>A	p.Lys115Lys	splice_region synonymous	Exon 5 of 12	NP_001137301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC68	ENST00000591504.6	TSL:1 MANE Select	c.345G>A	p.Lys115Lys	splice_region synonymous	Exon 5 of 12	ENSP00000466690.1
	CCDC68	ENST00000432185.5	TSL:1	c.345G>A	p.Lys115Lys	splice_region synonymous	Exon 3 of 10	ENSP00000413406.1
	CCDC68	ENST00000337363.8	TSL:2	c.345G>A	p.Lys115Lys	splice_region synonymous	Exon 5 of 12	ENSP00000337209.3

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

GnomAD2 exomes AF: 0.202 AC: 49560 AN: 245240 AF XY: 0.207

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 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

African (AFR) AF: 0.0352 AC: 1163 AN: 33076

American (AMR) AF: 0.110 AC: 4802 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6741 AN: 25920

East Asian (EAS) AF: 0.347 AC: 13746 AN: 39576

South Asian (SAS) AF: 0.192 AC: 16319 AN: 84816

European-Finnish (FIN) AF: 0.231 AC: 12302 AN: 53264

Middle Eastern (MID) AF: 0.207 AC: 1187 AN: 5736

European-Non Finnish (NFE) AF: 0.229 AC: 254153 AN: 1107982

Other (OTH) AF: 0.221 AC: 13257 AN: 60018

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

African (AFR) AF: 0.0417 AC: 1732 AN: 41534

American (AMR) AF: 0.158 AC: 2420 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5170

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4828

European-Finnish (FIN) AF: 0.229 AC: 2421 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15766 AN: 67978

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.213 Hom.: 9786

Bravo AF: 0.162

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.82
PhyloP100		4.0
Mutation Taster		=23/77	polymorphism (auto)

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

Other links and lift over

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