rs1060502867

Variant names:

• chr3-180616948-C-G
• rs1060502867
• NM_181426.2:c.2284G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-180616948-C-G
• chr3-180616948-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181426.2(CCDC39):​c.2284G>C​(p.Asp762His) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. 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. D762N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119678676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181426.2. 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
	CCDC39	NM_181426.2	MANE Select	c.2284G>C	p.Asp762His	missense	Exon 17 of 20	NP_852091.1	Q9UFE4-1
	TTC14	NM_001288582.2		c.1775-432C>G		intron	N/A	NP_001275511.1	Q96N46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.2284G>C	p.Asp762His	missense	Exon 17 of 20	ENSP00000417960.2	Q9UFE4-1
	TTC14	ENST00000382584.8	TSL:1	c.1775-432C>G		intron	N/A	ENSP00000372027.4	Q96N46-2
	CCDC39	ENST00000936067.1		c.2191G>C	p.Asp731His	missense	Exon 16 of 19	ENSP00000606126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.67
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.29
Sift	Benign	0.034	D
Sift4G	Uncertain	0.018	D
Polyphen		0.90	P
Vest4		0.22
MutPred		0.13		Gain of catalytic residue at L761 (P = 0.175)
MVP		0.39
MPC		0.074
ClinPred		0.24	T
GERP RS		-0.58
PromoterAI		0.00080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1060502867; hg19: chr3-180334736;