rs115647631

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000420323.7(DNAH1):ā€‹c.10616A>Gā€‹(p.Lys3539Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,614,038 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00092 ( 1 hom., cov: 32)
Exomes š‘“: 0.000077 ( 1 hom. )

Consequence

DNAH1
ENST00000420323.7 missense

Scores

1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.011842728).
BP6
Variant 3-52393475-A-G is Benign according to our data. Variant chr3-52393475-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 544674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH1NM_015512.5 linkuse as main transcriptc.10616A>G p.Lys3539Arg missense_variant 66/78 ENST00000420323.7 NP_056327.4
DNAH1XM_017006129.2 linkuse as main transcriptc.10685A>G p.Lys3562Arg missense_variant 68/80 XP_016861618.1
DNAH1XM_017006130.2 linkuse as main transcriptc.10616A>G p.Lys3539Arg missense_variant 67/79 XP_016861619.1
DNAH1XM_017006131.2 linkuse as main transcriptc.10559A>G p.Lys3520Arg missense_variant 67/79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkuse as main transcriptc.10616A>G p.Lys3539Arg missense_variant 66/781 NM_015512.5 ENSP00000401514 P1Q9P2D7-4
DNAH1ENST00000486752.5 linkuse as main transcriptn.11073A>G non_coding_transcript_exon_variant 65/772
DNAH1ENST00000488988.5 linkuse as main transcriptn.2402A>G non_coding_transcript_exon_variant 13/252
DNAH1ENST00000490713.5 linkuse as main transcriptc.1316A>G p.Lys439Arg missense_variant, NMD_transcript_variant 9/205 ENSP00000419071

Frequencies

GnomAD3 genomes
AF:
0.000920
AC:
140
AN:
152242
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
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:
0.000956
GnomAD3 exomes
AF:
0.000185
AC:
46
AN:
249164
Hom.:
0
AF XY:
0.000163
AC XY:
22
AN XY:
135202
show subpopulations
Gnomad AFR exome
AF:
0.00239
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.0000773
AC:
113
AN:
1461678
Hom.:
1
Cov.:
32
AF XY:
0.0000660
AC XY:
48
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00221
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000919
AC:
140
AN:
152360
Hom.:
1
Cov.:
32
AF XY:
0.000846
AC XY:
63
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00286
Gnomad4 AMR
AF:
0.00118
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:
0.000946
Alfa
AF:
0.000197
Hom.:
0
Bravo
AF:
0.00114
ESP6500AA
AF:
0.00266
AC:
11
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000231
AC:
28
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 08, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
19
DANN
Benign
0.97
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.012
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.91
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.062
Sift
Benign
0.46
T
Sift4G
Benign
0.51
T
Vest4
0.23
MVP
0.42
MPC
0.10
ClinPred
0.020
T
GERP RS
3.3
gMVP
0.35

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: rs115647631; hg19: chr3-52427491; API