Menu
GeneBe

rs149285738

chr3-52364691-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_015512.5(DNAH1):c.5298G>A(p.Gly1766=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,613,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26
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 -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-52364691-G-A is Benign according to our data. Variant chr3-52364691-G-A is described in ClinVar as [Benign]. Clinvar id is 544648.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.26 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH1NM_015512.5 linkuse as main transcriptc.5298G>A p.Gly1766= synonymous_variant 33/78 ENST00000420323.7
DNAH1XM_017006129.2 linkuse as main transcriptc.5298G>A p.Gly1766= synonymous_variant 34/80
DNAH1XM_017006130.2 linkuse as main transcriptc.5298G>A p.Gly1766= synonymous_variant 34/79
DNAH1XM_017006131.2 linkuse as main transcriptc.5298G>A p.Gly1766= synonymous_variant 34/79

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH1ENST00000420323.7 linkuse as main transcriptc.5298G>A p.Gly1766= synonymous_variant 33/781 NM_015512.5 P1Q9P2D7-4
DNAH1ENST00000486752.5 linkuse as main transcriptn.5559G>A non_coding_transcript_exon_variant 33/772

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000317
AC:
79
AN:
249000
Hom.:
0
AF XY:
0.000333
AC XY:
45
AN XY:
135100
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00398
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000230
Gnomad OTH exome
AF:
0.000828
GnomAD4 exome
AF:
0.000216
AC:
316
AN:
1461616
Hom.:
1
Cov.:
31
AF XY:
0.000243
AC XY:
177
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00459
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.0000980
Gnomad4 OTH exome
AF:
0.000547
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00230
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000393
Hom.:
0
Bravo
AF:
0.000234
EpiCase
AF:
0.000545
EpiControl
AF:
0.000415

ClinVar

Significance: 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
Benign, criteria provided, single submitterclinical testingInvitaeJan 26, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
7.0
Dann
Benign
0.69

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: rs149285738; hg19: chr3-52398707; API