chr3-52392868-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015512.5(DNAH1):​c.10317C>T​(p.Ile3439Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,608,620 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 141 hom., cov: 30)
Exomes 𝑓: 0.045 ( 1646 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.67
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 3-52392868-C-T is Benign according to our data. Variant chr3-52392868-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0381 (5666/148804) while in subpopulation NFE AF= 0.0494 (3323/67324). AF 95% confidence interval is 0.048. There are 141 homozygotes in gnomad4. There are 2595 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 141 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH1NM_015512.5 linkc.10317C>T p.Ile3439Ile synonymous_variant Exon 65 of 78 ENST00000420323.7 NP_056327.4 Q9P2D7-4A0A140VJI6
DNAH1XM_017006129.2 linkc.10386C>T p.Ile3462Ile synonymous_variant Exon 67 of 80 XP_016861618.1
DNAH1XM_017006130.2 linkc.10317C>T p.Ile3439Ile synonymous_variant Exon 66 of 79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkc.10260C>T p.Ile3420Ile synonymous_variant Exon 66 of 79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkc.10317C>T p.Ile3439Ile synonymous_variant Exon 65 of 78 1 NM_015512.5 ENSP00000401514.2 Q9P2D7-4
DNAH1ENST00000486752.5 linkn.10774C>T non_coding_transcript_exon_variant Exon 64 of 77 2
DNAH1ENST00000488988.5 linkn.2103C>T non_coding_transcript_exon_variant Exon 12 of 25 2
DNAH1ENST00000490713.5 linkn.1017C>T non_coding_transcript_exon_variant Exon 8 of 20 5 ENSP00000419071.1 H7C563

Frequencies

GnomAD3 genomes
AF:
0.0381
AC:
5665
AN:
148688
Hom.:
140
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0206
Gnomad AMI
AF:
0.0837
Gnomad AMR
AF:
0.0487
Gnomad ASJ
AF:
0.0298
Gnomad EAS
AF:
0.0208
Gnomad SAS
AF:
0.0216
Gnomad FIN
AF:
0.0310
Gnomad MID
AF:
0.0387
Gnomad NFE
AF:
0.0494
Gnomad OTH
AF:
0.0432
GnomAD3 exomes
AF:
0.0373
AC:
9259
AN:
248252
Hom.:
217
AF XY:
0.0375
AC XY:
5054
AN XY:
134748
show subpopulations
Gnomad AFR exome
AF:
0.0218
Gnomad AMR exome
AF:
0.0340
Gnomad ASJ exome
AF:
0.0289
Gnomad EAS exome
AF:
0.0178
Gnomad SAS exome
AF:
0.0193
Gnomad FIN exome
AF:
0.0322
Gnomad NFE exome
AF:
0.0497
Gnomad OTH exome
AF:
0.0472
GnomAD4 exome
AF:
0.0453
AC:
66152
AN:
1459816
Hom.:
1646
Cov.:
40
AF XY:
0.0449
AC XY:
32611
AN XY:
726106
show subpopulations
Gnomad4 AFR exome
AF:
0.0230
Gnomad4 AMR exome
AF:
0.0369
Gnomad4 ASJ exome
AF:
0.0300
Gnomad4 EAS exome
AF:
0.0167
Gnomad4 SAS exome
AF:
0.0198
Gnomad4 FIN exome
AF:
0.0334
Gnomad4 NFE exome
AF:
0.0502
Gnomad4 OTH exome
AF:
0.0466
GnomAD4 genome
AF:
0.0381
AC:
5666
AN:
148804
Hom.:
141
Cov.:
30
AF XY:
0.0359
AC XY:
2595
AN XY:
72374
show subpopulations
Gnomad4 AFR
AF:
0.0205
Gnomad4 AMR
AF:
0.0487
Gnomad4 ASJ
AF:
0.0298
Gnomad4 EAS
AF:
0.0204
Gnomad4 SAS
AF:
0.0214
Gnomad4 FIN
AF:
0.0310
Gnomad4 NFE
AF:
0.0494
Gnomad4 OTH
AF:
0.0451
Alfa
AF:
0.0486
Hom.:
254
Bravo
AF:
0.0395
Asia WGS
AF:
0.0360
AC:
123
AN:
3478
EpiCase
AF:
0.0501
EpiControl
AF:
0.0544

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 09, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
1.4
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs419050; hg19: chr3-52426884; API