16-20933237-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001347886.2(DNAH3):c.12130C>T(p.Leu4044Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
DNAH3
NM_001347886.2 missense
NM_001347886.2 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 3.03
Genes affected
DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.37525892).
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH3 | NM_001347886.2 | c.12130C>T | p.Leu4044Phe | missense_variant | 62/62 | ENST00000698260.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH3 | ENST00000698260.1 | c.12130C>T | p.Leu4044Phe | missense_variant | 62/62 | NM_001347886.2 | P1 | ||
DNAH3 | ENST00000261383.3 | c.12268C>T | p.Leu4090Phe | missense_variant | 62/62 | 1 | |||
DNAH3 | ENST00000685858.1 | c.12310C>T | p.Leu4104Phe | missense_variant | 62/62 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152242Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251454Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135900
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GnomAD4 exome AF: 0.000106 AC: 155AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 74AN XY: 727248
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74390
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.12268C>T (p.L4090F) alteration is located in exon 62 (coding exon 62) of the DNAH3 gene. This alteration results from a C to T substitution at nucleotide position 12268, causing the leucine (L) at amino acid position 4090 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at