rs6769457

Variant names:

• chr3-180648168-G-A
• rs6769457
• NM_181426.2:c.1359C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-180648168-G-A
• chr3-180648168-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_181426.2(CCDC39):​c.1359C>T​(p.Ser453Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,604,550 control chromosomes in the GnomAD database, including 54,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (11653 hom., cov: 31)
  • Exomes 𝑓: 0.23 (42897 hom.)
• Consequence: CCDC39 NM_181426.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.458
• Publications: 9 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-180648168-G-A is Benign according to our data. Variant chr3-180648168-G-A is described in ClinVar as Benign. ClinVar VariationId is 162842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.458 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 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.1359C>T	p.Ser453Ser	synonymous	Exon 10 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.1359C>T	p.Ser453Ser	synonymous	Exon 10 of 20	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.1266C>T	p.Ser422Ser	synonymous	Exon 9 of 19	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.1167C>T	p.Ser389Ser	synonymous	Exon 9 of 19	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51594 AN: 151802 Hom.: 11614 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00521

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.236 AC: 58117 AN: 246654 AF XY: 0.229

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.00331

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.228 AC: 331630 AN: 1452630 Hom.: 42897 Cov.: 29 AF XY: 0.226 AC XY: 163194 AN XY: 722888

African (AFR) AF: 0.667 AC: 22122 AN: 33156

American (AMR) AF: 0.239 AC: 10645 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4896 AN: 26050

East Asian (EAS) AF: 0.00212 AC: 84 AN: 39578

South Asian (SAS) AF: 0.203 AC: 17462 AN: 85910

European-Finnish (FIN) AF: 0.239 AC: 12709 AN: 53206

Middle Eastern (MID) AF: 0.278 AC: 1560 AN: 5612

European-Non Finnish (NFE) AF: 0.224 AC: 247706 AN: 1104600

Other (OTH) AF: 0.241 AC: 14446 AN: 60000

GnomAD4 genome AF: 0.340 AC: 51700 AN: 151920 Hom.: 11653 Cov.: 31 AF XY: 0.335 AC XY: 24879 AN XY: 74254

African (AFR) AF: 0.644 AC: 26674 AN: 41410

American (AMR) AF: 0.294 AC: 4483 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3470

East Asian (EAS) AF: 0.00522 AC: 27 AN: 5172

South Asian (SAS) AF: 0.183 AC: 883 AN: 4814

European-Finnish (FIN) AF: 0.235 AC: 2475 AN: 10546

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15479 AN: 67930

Other (OTH) AF: 0.319 AC: 671 AN: 2102

Alfa AF: 0.269 Hom.: 19012

Bravo AF: 0.357

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	2	Primary ciliary dyskinesia 14 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.8
DANN	Benign	0.58
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6769457; hg19: chr3-180365956; COSMIC: COSV56496618;