NM_181426.2:c.2301G>A

Variant names:

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

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.2301G>A​(p.Leu767Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,483,642 control chromosomes in the GnomAD database, including 3,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L767L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.092 (1063 hom., cov: 32)
  • Exomes 𝑓: 0.045 (2099 hom.)
• Consequence: CCDC39 NM_181426.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.742
• Publications: 7 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-180616931-C-T is Benign according to our data. Variant chr3-180616931-C-T is described in ClinVar as Benign. ClinVar VariationId is 162840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.742 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 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.2301G>A	p.Leu767Leu	synonymous	Exon 17 of 20	NP_852091.1	Q9UFE4-1
	TTC14	NM_001288582.2		c.1775-449C>T		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>A	p.Leu767Leu	synonymous	Exon 17 of 20	ENSP00000417960.2	Q9UFE4-1
	TTC14	ENST00000382584.8	TSL:1	c.1775-449C>T		intron	N/A	ENSP00000372027.4	Q96N46-2
	CCDC39	ENST00000936067.1		c.2208G>A	p.Leu736Leu	synonymous	Exon 16 of 19	ENSP00000606126.1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13990 AN: 151942 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.00728

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0852

GnomAD2 exomes AF: 0.0556 AC: 11959 AN: 215174 AF XY: 0.0562

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.0555

Gnomad EAS exome AF: 0.00157

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.0459

Gnomad OTH exome AF: 0.0678

GnomAD4 exome AF: 0.0450 AC: 59959 AN: 1331582 Hom.: 2099 Cov.: 24 AF XY: 0.0464 AC XY: 30909 AN XY: 665944

African (AFR) AF: 0.211 AC: 6279 AN: 29786

American (AMR) AF: 0.0472 AC: 1909 AN: 40406

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 1273 AN: 24954

East Asian (EAS) AF: 0.00101 AC: 39 AN: 38740

South Asian (SAS) AF: 0.0829 AC: 6529 AN: 78760

European-Finnish (FIN) AF: 0.00714 AC: 365 AN: 51130

Middle Eastern (MID) AF: 0.107 AC: 589 AN: 5496

European-Non Finnish (NFE) AF: 0.0395 AC: 39774 AN: 1006492

Other (OTH) AF: 0.0574 AC: 3202 AN: 55818

GnomAD4 genome AF: 0.0923 AC: 14029 AN: 152060 Hom.: 1063 Cov.: 32 AF XY: 0.0890 AC XY: 6614 AN XY: 74336

African (AFR) AF: 0.212 AC: 8796 AN: 41430

American (AMR) AF: 0.0751 AC: 1147 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 185 AN: 3462

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5192

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4824

European-Finnish (FIN) AF: 0.00728 AC: 77 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3080 AN: 67980

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0617 Hom.: 459

Bravo AF: 0.101

Asia WGS AF: 0.0730 AC: 252 AN: 3474

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		0.74
PromoterAI		-0.0099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;