3-180647255-TAA-TAAAA

Position:

• chr3-180647255-TAA-TAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_181426.2(CCDC39):​c.1363-13_1363-12insTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,284,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00064 (0 hom.)
• Consequence: CCDC39 NM_181426.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-180647255-T-TAA is Benign according to our data. Variant chr3-180647255-T-TAA is described in ClinVar as [Benign]. Clinvar id is 2896815.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC39	NM_181426.2	c.1363-13_1363-12insTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000476379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC39	ENST00000476379.6	c.1363-13_1363-12insTT		splice_polypyrimidine_tract_variant, intron_variant		2	NM_181426.2	P2

Frequencies

GnomAD3 genomes AF: 0.00000692 AC: 1 AN: 144554 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000641 AC: 731 AN: 1140046 Hom.: 0 Cov.: 24 AF XY: 0.000691 AC XY: 388 AN XY: 561670

Gnomad4 AFR exome AF: 0.000126

Gnomad4 AMR exome AF: 0.000820

Gnomad4 ASJ exome AF: 0.000692

Gnomad4 EAS exome AF: 0.0000354

Gnomad4 SAS exome AF: 0.000590

Gnomad4 FIN exome AF: 0.000969

Gnomad4 NFE exome AF: 0.000656

Gnomad4 OTH exome AF: 0.000646

GnomAD4 genome AF: 0.00000692 AC: 1 AN: 144554 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 70092

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs374074877; hg19: chr3-180365043;