3-52375405-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015512.5(DNAH1):ā€‹c.7151A>Gā€‹(p.Asn2384Ser) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,612,530 control chromosomes in the GnomAD database, including 10,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.078 ( 616 hom., cov: 32)
Exomes š‘“: 0.11 ( 10191 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.77
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 (MetaRNN=0.0019221604).
BP6
Variant 3-52375405-A-G is Benign according to our data. Variant chr3-52375405-A-G is described in ClinVar as [Benign]. Clinvar id is 402602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH1NM_015512.5 linkuse as main transcriptc.7151A>G p.Asn2384Ser missense_variant 45/78 ENST00000420323.7 NP_056327.4
DNAH1XM_017006129.2 linkuse as main transcriptc.7220A>G p.Asn2407Ser missense_variant 47/80 XP_016861618.1
DNAH1XM_017006130.2 linkuse as main transcriptc.7151A>G p.Asn2384Ser missense_variant 46/79 XP_016861619.1
DNAH1XM_017006131.2 linkuse as main transcriptc.7220A>G p.Asn2407Ser missense_variant 47/79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkuse as main transcriptc.7151A>G p.Asn2384Ser missense_variant 45/781 NM_015512.5 ENSP00000401514 P1Q9P2D7-4
DNAH1ENST00000486752.5 linkuse as main transcriptn.7412A>G non_coding_transcript_exon_variant 45/772

Frequencies

GnomAD3 genomes
AF:
0.0779
AC:
11851
AN:
152166
Hom.:
617
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0200
Gnomad AMI
AF:
0.0713
Gnomad AMR
AF:
0.0742
Gnomad ASJ
AF:
0.126
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.0660
Gnomad FIN
AF:
0.0526
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.121
Gnomad OTH
AF:
0.102
GnomAD3 exomes
AF:
0.0836
AC:
20628
AN:
246688
Hom.:
1040
AF XY:
0.0848
AC XY:
11357
AN XY:
133862
show subpopulations
Gnomad AFR exome
AF:
0.0179
Gnomad AMR exome
AF:
0.0634
Gnomad ASJ exome
AF:
0.119
Gnomad EAS exome
AF:
0.000279
Gnomad SAS exome
AF:
0.0720
Gnomad FIN exome
AF:
0.0566
Gnomad NFE exome
AF:
0.117
Gnomad OTH exome
AF:
0.0913
GnomAD4 exome
AF:
0.112
AC:
163898
AN:
1460246
Hom.:
10191
Cov.:
32
AF XY:
0.111
AC XY:
80613
AN XY:
726340
show subpopulations
Gnomad4 AFR exome
AF:
0.0188
Gnomad4 AMR exome
AF:
0.0663
Gnomad4 ASJ exome
AF:
0.120
Gnomad4 EAS exome
AF:
0.000328
Gnomad4 SAS exome
AF:
0.0751
Gnomad4 FIN exome
AF:
0.0593
Gnomad4 NFE exome
AF:
0.127
Gnomad4 OTH exome
AF:
0.105
GnomAD4 genome
AF:
0.0778
AC:
11847
AN:
152284
Hom.:
616
Cov.:
32
AF XY:
0.0751
AC XY:
5592
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0200
Gnomad4 AMR
AF:
0.0741
Gnomad4 ASJ
AF:
0.126
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.0667
Gnomad4 FIN
AF:
0.0526
Gnomad4 NFE
AF:
0.121
Gnomad4 OTH
AF:
0.101
Alfa
AF:
0.113
Hom.:
1497
Bravo
AF:
0.0763
TwinsUK
AF:
0.130
AC:
483
ALSPAC
AF:
0.127
AC:
491
ESP6500AA
AF:
0.0183
AC:
76
ESP6500EA
AF:
0.122
AC:
1026
ExAC
AF:
0.0828
AC:
10023
Asia WGS
AF:
0.0260
AC:
93
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
13
DANN
Benign
0.67
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.73
T
MetaRNN
Benign
0.0019
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.28
T
PROVEAN
Benign
1.0
N
REVEL
Benign
0.059
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.052
MPC
0.098
ClinPred
0.0017
T
GERP RS
2.9
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs56002041; hg19: chr3-52409421; COSMIC: COSV70229077; COSMIC: COSV70229077; API