rs4930721

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001372106.1(DNAH10):​c.13308C>G​(p.Ser4436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S4436S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

DNAH10
NM_001372106.1 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63
Variant links:
Genes affected
DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]
DNAH10OS (HGNC:37121): (dynein axonemal heavy chain 10 opposite strand)
CCDC92 (HGNC:29563): (coiled-coil domain containing 92) Enables identical protein binding activity. Located in centriole; centrosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAH10. . Gene score misZ 1.5457 (greater than the threshold 3.09). Trascript score misZ 3.4903 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 56.
BP4
Computational evidence support a benign effect (MetaRNN=0.11142519).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH10NM_001372106.1 linkuse as main transcriptc.13308C>G p.Ser4436Arg missense_variant 77/79 ENST00000673944.1 NP_001359035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH10ENST00000673944.1 linkuse as main transcriptc.13308C>G p.Ser4436Arg missense_variant 77/79 NM_001372106.1 ENSP00000501095 P1
DNAH10OSENST00000514254.3 linkuse as main transcriptn.920+723G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.0020
DANN
Benign
0.95
DEOGEN2
Benign
0.031
.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.050
.;N
MutationTaster
Benign
0.96
P
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.8
D;.
REVEL
Benign
0.050
Sift
Benign
0.43
T;.
Polyphen
0.033
.;B
MutPred
0.63
.;Gain of solvent accessibility (P = 0.0365);
MVP
0.040
MPC
0.19
ClinPred
0.63
D
GERP RS
-9.1
Varity_R
0.30
gMVP
0.64

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

LitVar

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

Other links and lift over

dbSNP: rs4930721; hg19: chr12-124417889; API