3-180679690-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000650889.1(CCDC39):​n.180T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 561,648 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 2 hom. )

Consequence

CCDC39
ENST00000650889.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.636
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 3-180679690-A-T is Benign according to our data. Variant chr3-180679690-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3342394.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (712/152212) while in subpopulation AFR AF= 0.0164 (680/41532). AF 95% confidence interval is 0.0154. There are 5 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC39NM_181426.2 linkc.-310T>A upstream_gene_variant ENST00000476379.6 NP_852091.1 Q9UFE4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC39ENST00000476379.6 linkc.-310T>A upstream_gene_variant 2 NM_181426.2 ENSP00000417960.2 Q9UFE4-1

Frequencies

GnomAD3 genomes
AF:
0.00467
AC:
711
AN:
152094
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00103
AC:
142
AN:
137682
Hom.:
0
AF XY:
0.000845
AC XY:
63
AN XY:
74590
show subpopulations
Gnomad AFR exome
AF:
0.0186
Gnomad AMR exome
AF:
0.000776
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000369
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000718
AC:
294
AN:
409436
Hom.:
2
Cov.:
0
AF XY:
0.000552
AC XY:
125
AN XY:
226372
show subpopulations
Gnomad4 AFR exome
AF:
0.0190
Gnomad4 AMR exome
AF:
0.000758
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000165
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000176
Gnomad4 OTH exome
AF:
0.00125
GnomAD4 genome
AF:
0.00468
AC:
712
AN:
152212
Hom.:
5
Cov.:
32
AF XY:
0.00476
AC XY:
354
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0164
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00252
Hom.:
0
Bravo
AF:
0.00518
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 10, 2022
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.4
DANN
Benign
0.39

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147114975; hg19: chr3-180397478; API