rs12163565

Positions:

chr3-52396510-G-A

Variant summary

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

The NM_015512.5(DNAH1):c.11402G>A(p.Gly3801Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,610,062 control chromosomes in the GnomAD database, including 33,361 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2538 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30823 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.05

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]

DNAH1 links:

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=0.0051918626).

BP6

Variant 3-52396510-G-A is Benign according to our data. Variant chr3-52396510-G-A is described in ClinVar as [Benign]. Clinvar id is 402604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAH1	NM_015512.5 linkuse as main transcript	c.11402G>A	p.Gly3801Asp	missense_variant	71/78	ENST00000420323.7
DNAH1	XM_017006129.2 linkuse as main transcript	c.11471G>A	p.Gly3824Asp	missense_variant	73/80
DNAH1	XM_017006130.2 linkuse as main transcript	c.11402G>A	p.Gly3801Asp	missense_variant	72/79
DNAH1	XM_017006131.2 linkuse as main transcript	c.11345G>A	p.Gly3782Asp	missense_variant	72/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.11402G>A	p.Gly3801Asp	missense_variant	71/78	1	NM_015512.5	P1	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.11859G>A		non_coding_transcript_exon_variant	70/77	2
DNAH1	ENST00000488988.5 linkuse as main transcript	n.3188G>A		non_coding_transcript_exon_variant	18/25	2
DNAH1	ENST00000490713.5 linkuse as main transcript	c.2102G>A	p.Gly701Asp	missense_variant, NMD_transcript_variant	14/20	5

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24503

AN:

151994

Hom.:

2539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.193

AC:

46753

AN:

242176

Hom.:

5005

AF XY:

0.200

AC XY:

26313

AN XY:

131590

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.0935

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.201

AC:

293354

AN:

1457950

Hom.:

30823

Cov.:

AF XY:

0.204

AC XY:

147697

AN XY:

724932

show subpopulations

Gnomad4 AFR exome

AF:

0.0371

Gnomad4 AMR exome

AF:

0.0976

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.161

AC:

24499

AN:

152112

Hom.:

2538

Cov.:

AF XY:

0.165

AC XY:

12280

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0469

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.197

Hom.:

6445

Bravo

AF:

0.147

TwinsUK

AF:

0.210

AC:

778

ALSPAC

AF:

0.201

AC:

773

ESP6500AA

AF:

0.0478

AC:

203

ESP6500EA

AF:

0.189

AC:

1603

ExAC

AF:

0.191

AC:

23105

Asia WGS

AF:

0.209

AC:

728

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant 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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Ciliary dyskinesia, primary, 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Spermatogenic failure 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.63

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.74

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

0.51

REVEL

Benign

0.041

Sift

Benign

0.69

Sift4G

Benign

1.0

Vest4

0.083

MPC

0.16

ClinPred

0.00093

GERP RS

2.4

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over