rs575350719

Variant names:

• chr3-180661957-C-A
• rs575350719
• NM_181426.2:c.261G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181426.2(CCDC39):​c.261G>T​(p.Lys87Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000098 in 1,561,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.391
• Publications: 1 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]

CCDC39 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 14

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000145075 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15069684).

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.261G>T	p.Lys87Asn	missense	Exon 3 of 20	NP_852091.1	Q9UFE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.261G>T	p.Lys87Asn	missense	Exon 3 of 20	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.261G>T	p.Lys87Asn	missense	Exon 3 of 19	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.261G>T	p.Lys87Asn	missense	Exon 3 of 19	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000234 AC: 4 AN: 171202 AF XY: 0.0000332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000580

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 144 AN: 1409248 Hom.: 0 Cov.: 31 AF XY: 0.0000991 AC XY: 69 AN XY: 695944

African (AFR) AF: 0.00 AC: 0 AN: 32286

American (AMR) AF: 0.00 AC: 0 AN: 36622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 37302

South Asian (SAS) AF: 0.00 AC: 0 AN: 79946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.000128 AC: 139 AN: 1083326

Other (OTH) AF: 0.0000856 AC: 5 AN: 58422

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74394

African (AFR) AF: 0.0000722 AC: 3 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000258 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.39
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.32
Sift	Benign	0.13	T
Sift4G	Benign	0.073	T
Polyphen		0.92	P
Vest4		0.65
MutPred		0.25		Loss of ubiquitination at K87 (P = 0.0039)
MVP		0.75
MPC		0.097
ClinPred		0.59	D
GERP RS		2.5
Varity_R		0.15
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: rs575350719; hg19: chr3-180379745;