rs112738198

Variant names:

• chr3-180659741-G-C
• rs112738198
• NM_181426.2:c.545C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-180659741-G-C
• chr3-180659741-G-A
• chr3-180659741-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_181426.2(CCDC39):​c.545C>G​(p.Thr182Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0318 in 1,610,888 control chromosomes in the GnomAD database, including 971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (73 hom., cov: 32)
  • Exomes 𝑓: 0.032 (898 hom.)
• Consequence: CCDC39 NM_181426.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.82
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033574104).
• BP6: Variant 3-180659741-G-C is Benign according to our data. Variant chr3-180659741-G-C is described in ClinVar as Benign. ClinVar VariationId is 162844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0251 (3828/152228) while in subpopulation NFE AF = 0.0391 (2660/67974). AF 95% confidence interval is 0.0379. There are 73 homozygotes in GnomAd4. There are 1820 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 AD,AR gene

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.545C>G	p.Thr182Ser	missense	Exon 5 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.545C>G	p.Thr182Ser	missense	Exon 5 of 20	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000651046.1		c.545C>G	p.Thr182Ser	missense	Exon 5 of 19	ENSP00000499175.1	A0A494C1Q3
	CCDC39	ENST00000936067.1		c.517-161C>G		intron	N/A	ENSP00000606126.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3828 AN: 152110 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00668

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.0241 AC: 5985 AN: 248098 AF XY: 0.0239

Gnomad AFR exome AF: 0.00530

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.00767

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0307

Gnomad NFE exome AF: 0.0384

Gnomad OTH exome AF: 0.0278

GnomAD4 exome AF: 0.0325 AC: 47386 AN: 1458660 Hom.: 898 Cov.: 31 AF XY: 0.0320 AC XY: 23217 AN XY: 725682

African (AFR) AF: 0.00568 AC: 190 AN: 33442

American (AMR) AF: 0.0150 AC: 672 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00858 AC: 224 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00583 AC: 502 AN: 86070

European-Finnish (FIN) AF: 0.0299 AC: 1580 AN: 52778

Middle Eastern (MID) AF: 0.00592 AC: 34 AN: 5746

European-Non Finnish (NFE) AF: 0.0384 AC: 42638 AN: 1110028

Other (OTH) AF: 0.0256 AC: 1546 AN: 60302

GnomAD4 genome AF: 0.0251 AC: 3828 AN: 152228 Hom.: 73 Cov.: 32 AF XY: 0.0244 AC XY: 1820 AN XY: 74446

African (AFR) AF: 0.00666 AC: 277 AN: 41570

American (AMR) AF: 0.0221 AC: 337 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3466

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4830

European-Finnish (FIN) AF: 0.0331 AC: 351 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2660 AN: 67974

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0310 Hom.: 70

Bravo AF: 0.0235

TwinsUK AF: 0.0388 AC: 144

ALSPAC AF: 0.0381 AC: 147

ESP6500AA AF: 0.00936 AC: 34

ESP6500EA AF: 0.0323 AC: 263

ExAC AF: 0.0245 AC: 2958

Asia WGS AF: 0.00115 AC: 4 AN: 3476

EpiCase AF: 0.0391

EpiControl AF: 0.0321

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.8
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.022	D
Sift4G	Benign	0.18	T
Polyphen		0.98	D
Vest4		0.15
MutPred		0.14		Gain of glycosylation at T182 (P = 0.096)
MPC		0.14
ClinPred		0.036	T
GERP RS		4.0
Varity_R		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs112738198; hg19: chr3-180377529; COSMIC: COSV107263997; COSMIC: COSV107263997;