chr3-180619294-G-C

Variant names:

• chr3-180619294-G-C
• rs61733579
• NM_181426.2:c.2230C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181426.2(CCDC39):​c.2230C>G​(p.Gln744Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,544,380 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (92 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (62 hom.)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.49
• Publications: 2 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: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000145075 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002523601).
• BP6: Variant 3-180619294-G-C is Benign according to our data. Variant chr3-180619294-G-C is described in ClinVar as Benign. ClinVar VariationId is 162841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

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.2230C>G	p.Gln744Glu	missense	Exon 16 of 20	NP_852091.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.2230C>G	p.Gln744Glu	missense	Exon 16 of 20	ENSP00000417960.2
	CCDC39	ENST00000936067.1		c.2137C>G	p.Gln713Glu	missense	Exon 15 of 19	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.2038C>G	p.Gln680Glu	missense	Exon 15 of 19	ENSP00000499175.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2643 AN: 151872 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00358 AC: 568 AN: 158672 AF XY: 0.00273

Gnomad AFR exome AF: 0.0599

Gnomad AMR exome AF: 0.00224

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000113

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.00155 AC: 2164 AN: 1392390 Hom.: 62 Cov.: 27 AF XY: 0.00132 AC XY: 910 AN XY: 687318

African (AFR) AF: 0.0580 AC: 1811 AN: 31246

American (AMR) AF: 0.00250 AC: 89 AN: 35536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.000139 AC: 11 AN: 78856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49128

Middle Eastern (MID) AF: 0.00142 AC: 8 AN: 5650

European-Non Finnish (NFE) AF: 0.0000438 AC: 47 AN: 1073466

Other (OTH) AF: 0.00343 AC: 198 AN: 57760

GnomAD4 genome AF: 0.0174 AC: 2642 AN: 151990 Hom.: 92 Cov.: 32 AF XY: 0.0162 AC XY: 1201 AN XY: 74314

African (AFR) AF: 0.0612 AC: 2538 AN: 41462

American (AMR) AF: 0.00419 AC: 64 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67902

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.00503 Hom.: 5

Bravo AF: 0.0194

ESP6500AA AF: 0.0516 AC: 181

ESP6500EA AF: 0.000250 AC: 2

ExAC AF: 0.00269 AC: 260

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0018	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.28
Sift	Benign	0.050	D
Sift4G	Benign	1.0	T
Polyphen		0.82	P
Vest4		0.22
MVP		0.93
MPC		0.14
ClinPred		0.012	T
GERP RS		4.5
Varity_R		0.19
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: rs61733579; hg19: chr3-180337082;