chr3-52370162-A-G

Position:

chr3-52370162-A-G

Variant summary

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

The ENST00000420323.7(DNAH1):c.6191A>G(p.Asn2064Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,844 control chromosomes in the GnomAD database, including 172 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 0.0094 ( 14 hom., cov: 33)

Exomes 𝑓: 0.011 ( 158 hom. )

Consequence

DNAH1
ENST00000420323.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.06

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=0.003696978).

BP6

Variant 3-52370162-A-G is Benign according to our data. Variant chr3-52370162-A-G is described in ClinVar as [Benign]. Clinvar id is 478474.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 = 0.00941 (1432/152190) while in subpopulation NFE AF= 0.00969 (659/67988). AF 95% confidence interval is 0.00908. There are 14 homozygotes in gnomad4. There are 826 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAH1	NM_015512.5 linkuse as main transcript	c.6191A>G	p.Asn2064Ser	missense_variant	39/78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2 linkuse as main transcript	c.6260A>G	p.Asn2087Ser	missense_variant	41/80		XP_016861618.1
DNAH1	XM_017006130.2 linkuse as main transcript	c.6191A>G	p.Asn2064Ser	missense_variant	40/79		XP_016861619.1
DNAH1	XM_017006131.2 linkuse as main transcript	c.6260A>G	p.Asn2087Ser	missense_variant	41/79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.6191A>G	p.Asn2064Ser	missense_variant	39/78	1	NM_015512.5	ENSP00000401514	P1	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.6452A>G		non_coding_transcript_exon_variant	39/77	2

Frequencies

GnomAD3 genomes

AF:

0.00941

AC:

1431

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0536

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0106

AC:

2640

AN:

249192

Hom.:

AF XY:

0.0110

AC XY:

1488

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.00626

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00644

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.00963

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0107

AC:

15670

AN:

1461654

Hom.:

158

Cov.:

AF XY:

0.0106

AC XY:

7702

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00704

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00674

Gnomad4 FIN exome

AF:

0.0479

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00941

AC:

1432

AN:

152190

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

826

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0536

Gnomad4 NFE

AF:

0.00969

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00864

Hom.:

Bravo

AF:

0.00618

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00231

AC:

ESP6500EA

AF:

0.00914

AC:

ExAC

AF:

0.0100

AC:

1214

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DNAH1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.021

Eigen_PC

Benign

0.061

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.87

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Uncertain

0.014

Sift4G

Uncertain

0.047

Vest4

0.43

MPC

0.12

ClinPred

0.032

GERP RS

4.5

gMVP

0.20

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.

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