3-180647255-TAA-TAAA

Variant names:

• chr3-180647255-T-TA
• rs374074877
• NM_181426.2:c.1363-13dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181426.2(CCDC39):​c.1363-13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,244,132 control chromosomes in the GnomAD database, including 4,949 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1558 hom., cov: 29)
  • Exomes 𝑓: 0.18 (3391 hom.)
• Consequence: CCDC39 NM_181426.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.273
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000145075 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-180647255-T-TA is Benign according to our data. Variant chr3-180647255-T-TA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 344267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 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.1363-13dupT		intron	N/A	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.1363-13_1363-12insT		intron	N/A	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.1270-13_1270-12insT		intron	N/A	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.1171-13_1171-12insT		intron	N/A	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 20333 AN: 144448 Hom.: 1557 Cov.: 29

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.228 AC: 17226 AN: 75564 AF XY: 0.231

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.0433

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.182 AC: 199677 AN: 1099620 Hom.: 3391 Cov.: 24 AF XY: 0.180 AC XY: 97507 AN XY: 541312

African (AFR) AF: 0.0906 AC: 2072 AN: 22872

American (AMR) AF: 0.173 AC: 3479 AN: 20106

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 3034 AN: 18022

East Asian (EAS) AF: 0.0169 AC: 451 AN: 26676

South Asian (SAS) AF: 0.138 AC: 7808 AN: 56686

European-Finnish (FIN) AF: 0.228 AC: 8920 AN: 39194

Middle Eastern (MID) AF: 0.140 AC: 631 AN: 4514

European-Non Finnish (NFE) AF: 0.191 AC: 165563 AN: 866948

Other (OTH) AF: 0.173 AC: 7719 AN: 44602

GnomAD4 genome AF: 0.141 AC: 20344 AN: 144512 Hom.: 1558 Cov.: 29 AF XY: 0.144 AC XY: 10090 AN XY: 70110

African (AFR) AF: 0.0732 AC: 2877 AN: 39312

American (AMR) AF: 0.183 AC: 2653 AN: 14472

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 482 AN: 3362

East Asian (EAS) AF: 0.00580 AC: 29 AN: 5000

South Asian (SAS) AF: 0.103 AC: 471 AN: 4586

European-Finnish (FIN) AF: 0.235 AC: 2098 AN: 8944

Middle Eastern (MID) AF: 0.126 AC: 35 AN: 278

European-Non Finnish (NFE) AF: 0.171 AC: 11227 AN: 65696

Other (OTH) AF: 0.156 AC: 308 AN: 1976

Alfa AF: 0.0812 Hom.: 89

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
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: rs374074877; hg19: chr3-180365043;