6-38923085-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001206927.2(DNAH8):ā€‹c.10690C>Gā€‹(p.Arg3564Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

2
13
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86
Variant links:
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH8NM_001206927.2 linkc.10690C>G p.Arg3564Gly missense_variant Exon 72 of 93 ENST00000327475.11 NP_001193856.1 Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH8ENST00000327475.11 linkc.10690C>G p.Arg3564Gly missense_variant Exon 72 of 93 5 NM_001206927.2 ENSP00000333363.7 A0A075B6F3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152034
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250582
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135436
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461186
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726900
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152034
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Benign
-0.0031
T
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.089
T;D;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.68
D;D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Uncertain
2.1
.;.;M
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-6.1
.;D;D
REVEL
Uncertain
0.50
Sift
Uncertain
0.014
.;D;D
Polyphen
1.0
.;.;D
Vest4
0.62
MutPred
0.37
.;.;Gain of ubiquitination at K3348 (P = 0.0371);
MVP
0.90
MPC
0.24
ClinPred
0.95
D
GERP RS
4.4
Varity_R
0.47
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs748121138; hg19: chr6-38890861; API