6-38923131-G-C

Variant summary

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

The NM_001206927.2(DNAH8):ā€‹c.10736G>Cā€‹(p.Gly3579Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,146 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‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

DNAH8
NM_001206927.2 missense

Scores

8
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.01
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.10736G>C p.Gly3579Ala 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.10736G>C p.Gly3579Ala missense_variant Exon 72 of 93 5 NM_001206927.2 ENSP00000333363.7 A0A075B6F3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;D;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Uncertain
0.39
D
MutationAssessor
Pathogenic
3.7
.;.;H
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.6
.;D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0020
.;D;D
Polyphen
1.0
.;.;D
Vest4
0.67
MutPred
0.51
.;.;Loss of ubiquitination at K3364 (P = 0.0618);
MVP
0.86
MPC
0.60
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.81
gMVP
0.54

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: rs1215830936; hg19: chr6-38890907; API