rs141651575

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001369.3(DNAH5):​c.1612G>C​(p.Glu538Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)

Consequence

DNAH5
NM_001369.3 missense

Scores

1
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.02
Variant links:
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.39877588).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH5NM_001369.3 linkuse as main transcriptc.1612G>C p.Glu538Gln missense_variant 12/79 ENST00000265104.5 NP_001360.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH5ENST00000265104.5 linkuse as main transcriptc.1612G>C p.Glu538Gln missense_variant 12/791 NM_001369.3 ENSP00000265104 P4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251202
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.068
T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.77
T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.11
Sift
Benign
0.47
T
Polyphen
0.036
B
Vest4
0.59
MutPred
0.44
Gain of ubiquitination at K542 (P = 0.1047);
MVP
0.65
MPC
0.40
ClinPred
0.92
D
GERP RS
5.6
Varity_R
0.55
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs141651575; hg19: chr5-13911527; API