rs561458801

Variant names:

• chr3-180616694-C-A
• rs561458801
• NM_181426.2:c.2408G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-180616694-C-A
• chr3-180616694-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181426.2(CCDC39):​c.2408G>T​(p.Cys803Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C803Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC39 NM_181426.2 missense, splice_region
• Scores: Splicing: ADA: 0.001662
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

Genes affected

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000145075 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.191358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2	c.2408G>T	p.Cys803Phe	missense_variant, splice_region_variant	Exon 18 of 20	ENST00000476379.6	NP_852091.1
TTC14	NM_001288582.2	c.1775-686C>A		intron_variant	Intron 12 of 12		NP_001275511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6	c.2408G>T	p.Cys803Phe	missense_variant, splice_region_variant	Exon 18 of 20	2	NM_181426.2	ENSP00000417960.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.0031	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.45
Sift	Benign	0.33	T
Sift4G	Benign	0.69	T
Polyphen		0.65	P
Vest4		0.44
MutPred		0.29		Gain of glycosylation at T800 (P = 0.0139);
MVP		0.64
MPC		0.096
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.077

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.086
SpliceAI score (max)		0.080		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: rs561458801; hg19: chr3-180334482;