rs1344011

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-54937957-C-A
• chr18-54937957-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_025214.3(CCDC68):​c.345G>T​(p.Lys115Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: not found (cov: 33)
• Consequence: CCDC68 NM_025214.3 missense, splice_region
• Scores: Splicing: ADA: 1.000
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

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>T	p.Lys115Asn	missense splice_region	Exon 5 of 12	NP_079490.1
	CCDC68	NM_001143829.2		c.345G>T	p.Lys115Asn	missense splice_region	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>T	p.Lys115Asn	missense splice_region	Exon 5 of 12	ENSP00000466690.1
	CCDC68	ENST00000432185.5	TSL:1	c.345G>T	p.Lys115Asn	missense splice_region	Exon 3 of 10	ENSP00000413406.1
	CCDC68	ENST00000337363.8	TSL:2	c.345G>T	p.Lys115Asn	missense splice_region	Exon 5 of 12	ENSP00000337209.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.23		Loss of ubiquitination at K115 (P = 0.0161)
MVP		0.76
MPC		0.21
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: 0

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

Other links and lift over

dbSNP: rs1344011; hg19: chr18-52605188;