rs188699424

Positions:

chr3-52346574-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015512.5(DNAH1):c.1759A>C(p.Asn587His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,614,056 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 6 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.769

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:

DNAH1 (HGNC:):

DNAH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006905675).

BP6

Variant 3-52346574-A-C is Benign according to our data. Variant chr3-52346574-A-C is described in ClinVar as [Benign]. Clinvar id is 478416.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000427 (65/152352) while in subpopulation EAS AF= 0.00887 (46/5184). AF 95% confidence interval is 0.00684. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5 linkuse as main transcript	c.1759A>C	p.Asn587His	missense_variant	11/78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 linkuse as main transcript	c.1759A>C	p.Asn587His	missense_variant	12/80		XP_016861618.1
DNAH1	XM_017006130.2 linkuse as main transcript	c.1759A>C	p.Asn587His	missense_variant	12/79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 linkuse as main transcript	c.1759A>C	p.Asn587His	missense_variant	12/79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.1759A>C	p.Asn587His	missense_variant	11/78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.2020A>C		non_coding_transcript_exon_variant	11/77	2
DNAH1	ENST00000497875.1 linkuse as main transcript	n.1924A>C		non_coding_transcript_exon_variant	12/21	2

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00905

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000790

AC:

197

AN:

249224

Hom.:

AF XY:

0.000754

AC XY:

102

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0102

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000220

AC:

322

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00534

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.000427

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00887

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000365

Hom.:

Bravo

AF:

0.000506

ExAC

AF:

0.000834

AC:

101

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

DNAH1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.14

Sift

Uncertain

0.017

Sift4G

Uncertain

0.020

Vest4

0.36

MVP

0.31

MPC

0.13

ClinPred

0.022

GERP RS

3.3

gMVP

0.44

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