3-180616835-C-T

Variant names:

• chr3-180616835-C-T
• rs7612917
• NM_181426.2:c.2397G>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.2397G>A​(p.Val799Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,606,498 control chromosomes in the GnomAD database, including 31,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2813 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28860 hom.)
• Consequence: CCDC39 NM_181426.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.448
• Publications: 10 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=-0.52).
• BP6: Variant 3-180616835-C-T is Benign according to our data. Variant chr3-180616835-C-T is described in ClinVar as Benign. ClinVar VariationId is 162839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.448 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	NM_181426.2	MANE Select	c.2397G>A	p.Val799Val	synonymous	Exon 17 of 20	NP_852091.1
	TTC14	NM_001288582.2		c.1775-545C>T		intron	N/A	NP_001275511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.2397G>A	p.Val799Val	synonymous	Exon 17 of 20	ENSP00000417960.2
	TTC14	ENST00000382584.8	TSL:1	c.1775-545C>T		intron	N/A	ENSP00000372027.4
	CCDC39	ENST00000651046.1		c.2205G>A	p.Val735Val	synonymous	Exon 16 of 19	ENSP00000499175.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28153 AN: 151998 Hom.: 2810 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.176 AC: 43280 AN: 246428 AF XY: 0.174

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.00145

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.194 AC: 282625 AN: 1454382 Hom.: 28860 Cov.: 30 AF XY: 0.192 AC XY: 138607 AN XY: 723594

African (AFR) AF: 0.153 AC: 5116 AN: 33336

American (AMR) AF: 0.184 AC: 8171 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3992 AN: 26036

East Asian (EAS) AF: 0.00106 AC: 42 AN: 39578

South Asian (SAS) AF: 0.124 AC: 10611 AN: 85774

European-Finnish (FIN) AF: 0.252 AC: 13336 AN: 52972

Middle Eastern (MID) AF: 0.166 AC: 953 AN: 5752

European-Non Finnish (NFE) AF: 0.207 AC: 229494 AN: 1106522

Other (OTH) AF: 0.182 AC: 10910 AN: 60100

GnomAD4 genome AF: 0.185 AC: 28177 AN: 152116 Hom.: 2813 Cov.: 32 AF XY: 0.185 AC XY: 13778 AN XY: 74348

African (AFR) AF: 0.160 AC: 6655 AN: 41520

American (AMR) AF: 0.200 AC: 3047 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3466

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5180

South Asian (SAS) AF: 0.112 AC: 539 AN: 4818

European-Finnish (FIN) AF: 0.248 AC: 2620 AN: 10582

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14177 AN: 67970

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.193 Hom.: 2256

Bravo AF: 0.179

Asia WGS AF: 0.0600 AC: 211 AN: 3476

EpiCase AF: 0.202

EpiControl AF: 0.198

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	-0.52
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		0.45
PromoterAI		-0.0081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs7612917; hg19: chr3-180334623;