16-20941474-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001347886.2(DNAH3):​c.11443A>G​(p.Met3815Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DNAH3
NM_001347886.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.675
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10771239).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH3NM_001347886.2 linkc.11443A>G p.Met3815Val missense_variant Exon 59 of 62 ENST00000698260.1 NP_001334815.1 Q8TD57A0A8V8TLI9B4E1S1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH3ENST00000698260.1 linkc.11443A>G p.Met3815Val missense_variant Exon 59 of 62 NM_001347886.2 ENSP00000513632.1 A0A8V8TLI9
DNAH3ENST00000261383.3 linkc.11581A>G p.Met3861Val missense_variant Exon 59 of 62 1 ENSP00000261383.3 Q8TD57-1
DNAH3ENST00000685858.1 linkc.11623A>G p.Met3875Val missense_variant Exon 59 of 62 ENSP00000508756.1 A0A8I5KSE2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
11
DANN
Benign
0.78
DEOGEN2
Benign
0.049
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.16
Sift
Benign
0.11
T
Polyphen
0.0
B
Vest4
0.18
MutPred
0.57
Gain of methylation at K3862 (P = 0.0332);
MVP
0.067
MPC
0.094
ClinPred
0.17
T
GERP RS
0.96
Varity_R
0.28
gMVP
0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-20952796; API