3-180616931-C-G

Variant names:

• chr3-180616931-C-G
• rs11914833
• NM_181426.2:c.2301G>C

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.2301G>C​(p.Leu767Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,334,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Synonymous variant affecting the same amino acid position (i.e. L767L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• 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=0.21674249).

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.2301G>C	p.Leu767Phe	missense	Exon 17 of 20	NP_852091.1	Q9UFE4-1
	TTC14	NM_001288582.2		c.1775-449C>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.2301G>C	p.Leu767Phe	missense	Exon 17 of 20	ENSP00000417960.2	Q9UFE4-1
	TTC14	ENST00000382584.8	TSL:1	c.1775-449C>G		intron	N/A	ENSP00000372027.4	Q96N46-2
	CCDC39	ENST00000936067.1		c.2208G>C	p.Leu736Phe	missense	Exon 16 of 19	ENSP00000606126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1334070 Hom.: 0 Cov.: 24 AF XY: 0.00000150 AC XY: 1 AN XY: 667124

African (AFR) AF: 0.00 AC: 0 AN: 29962

American (AMR) AF: 0.00 AC: 0 AN: 40422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24972

East Asian (EAS) AF: 0.00 AC: 0 AN: 38742

South Asian (SAS) AF: 0.00 AC: 0 AN: 78882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 9.92e-7 AC: 1 AN: 1008542

Other (OTH) AF: 0.00 AC: 0 AN: 55906

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	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.74
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.26
Sift	Benign	0.051	T
Sift4G	Uncertain	0.041	D
Polyphen		0.81	P
Vest4		0.25
MutPred		0.23		Gain of methylation at K772 (P = 0.1322)
MVP		0.36
MPC		0.070
ClinPred		0.34	T
GERP RS		4.8
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.043
Mutation Taster		=99/1	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: rs11914833; hg19: chr3-180334719;