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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. K115K) has been classified as Uncertain significance.

• 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

Sel.	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	Q9H2F9
	CCDC68	NM_001143829.2		c.345G>T	p.Lys115Asn	missense splice_region	Exon 5 of 12	NP_001137301.1	Q9H2F9

Ensembl Transcripts

Sel.	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	Q9H2F9
	CCDC68	ENST00000432185.5	TSL:1	c.345G>T	p.Lys115Asn	missense splice_region	Exon 3 of 10	ENSP00000413406.1	Q9H2F9
	CCDC68	ENST00000337363.8	TSL:2	c.345G>T	p.Lys115Asn	missense splice_region	Exon 5 of 12	ENSP00000337209.3	Q9H2F9

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;