rs145107574

Variant summary

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

The NM_001206927.2(DNAH8):ā€‹c.9643A>Cā€‹(p.Asn3215His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.397
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]

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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=0.10972598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH8NM_001206927.2 linkuse as main transcriptc.9643A>C p.Asn3215His missense_variant 65/93 ENST00000327475.11 NP_001193856.1
DNAH8-AS1NR_038401.1 linkuse as main transcriptn.783-1810T>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH8ENST00000327475.11 linkuse as main transcriptc.9643A>C p.Asn3215His missense_variant 65/935 NM_001206927.2 ENSP00000333363 P2
DNAH8ENST00000359357.7 linkuse as main transcriptc.8992A>C p.Asn2998His missense_variant 63/912 ENSP00000352312 A2Q96JB1-1
DNAH8ENST00000449981.6 linkuse as main transcriptc.9643A>C p.Asn3215His missense_variant 64/825 ENSP00000415331

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251180
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461830
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
11
DANN
Benign
0.95
DEOGEN2
Benign
0.030
T;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.68
.;.;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-2.2
.;N;N
REVEL
Benign
0.049
Sift
Benign
0.12
.;T;T
Polyphen
0.0050
.;.;B
Vest4
0.39
MutPred
0.48
.;.;Gain of helix (P = 0.0325);
MVP
0.69
MPC
0.13
ClinPred
0.035
T
GERP RS
3.2
Varity_R
0.12
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs145107574; hg19: chr6-38877423; API