rs866647249

Variant summary

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

The NM_015512.5(DNAH1):​c.10688C>A​(p.Pro3563Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DNAH1
NM_015512.5 missense

Scores

1
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.488
Variant links:
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

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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=0.28199154).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH1NM_015512.5 linkc.10688C>A p.Pro3563Gln missense_variant 67/78 ENST00000420323.7 NP_056327.4 Q9P2D7-4A0A140VJI6
DNAH1XM_017006129.2 linkc.10757C>A p.Pro3586Gln missense_variant 69/80 XP_016861618.1
DNAH1XM_017006130.2 linkc.10688C>A p.Pro3563Gln missense_variant 68/79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkc.10631C>A p.Pro3544Gln missense_variant 68/79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkc.10688C>A p.Pro3563Gln missense_variant 67/781 NM_015512.5 ENSP00000401514.2 Q9P2D7-4
DNAH1ENST00000486752.5 linkn.11145C>A non_coding_transcript_exon_variant 66/772
DNAH1ENST00000488988.5 linkn.2474C>A non_coding_transcript_exon_variant 14/252
DNAH1ENST00000490713.5 linkn.1388C>A non_coding_transcript_exon_variant 10/205 ENSP00000419071.1 H7C563

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
11
DANN
Uncertain
0.99
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.86
D
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.28
T
MetaSVM
Uncertain
-0.21
T
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.029
D
Vest4
0.39
MutPred
0.51
Loss of glycosylation at P3563 (P = 0.0722);
MVP
0.41
MPC
0.19
ClinPred
0.91
D
GERP RS
0.55
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs866647249; hg19: chr3-52428542; API