rs876657752

Variant names:

• chr3-180619286-T-A
• rs876657752
• NM_181426.2:c.2238A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-180619286-T-A
• chr3-180619286-T-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_181426.2(CCDC39):​c.2238A>T​(p.Gln746His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,543,140 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.215
• 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]

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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29297847).

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.2238A>T	p.Gln746His	missense	Exon 16 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.2238A>T	p.Gln746His	missense	Exon 16 of 20	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.2145A>T	p.Gln715His	missense	Exon 15 of 19	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.2046A>T	p.Gln682His	missense	Exon 15 of 19	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000251 AC: 4 AN: 159212 AF XY: 0.0000119

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: 0.0000641

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 41 AN: 1391004 Hom.: 0 Cov.: 27 AF XY: 0.0000248 AC XY: 17 AN XY: 686754

African (AFR) AF: 0.00 AC: 0 AN: 31382

American (AMR) AF: 0.00 AC: 0 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25092

East Asian (EAS) AF: 0.00 AC: 0 AN: 35810

South Asian (SAS) AF: 0.00 AC: 0 AN: 78948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.0000373 AC: 40 AN: 1071598

Other (OTH) AF: 0.0000173 AC: 1 AN: 57724

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.21
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.17		Loss of MoRF binding (P = 0.1211)
MVP		0.90
MPC		0.32
ClinPred		0.72	D
GERP RS		2.9
Varity_R		0.12
Mutation Taster		=97/3	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: rs876657752; hg19: chr3-180337074;