Variant chr3-52394972-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015512.5(DNAH1):c.10881C>A(p.Val3627=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,930 control chromosomes in the GnomAD database, including 10,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 613 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10034 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.81

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 3-52394972-C-A is Benign according to our data. Variant chr3-52394972-C-A is described in ClinVar as [Benign]. Clinvar id is 402603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAH1	NM_015512.5 linkuse as main transcript	c.10881C>A	p.Val3627=	synonymous_variant	68/78	ENST00000420323.7
DNAH1	XM_017006129.2 linkuse as main transcript	c.10950C>A	p.Val3650=	synonymous_variant	70/80
DNAH1	XM_017006130.2 linkuse as main transcript	c.10881C>A	p.Val3627=	synonymous_variant	69/79
DNAH1	XM_017006131.2 linkuse as main transcript	c.10824C>A	p.Val3608=	synonymous_variant	69/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.10881C>A	p.Val3627=	synonymous_variant	68/78	1	NM_015512.5	P1	Q9P2D7-4

Frequencies

GnomAD3 genomes

AF:

0.0770

AC:

11716

AN:

152194

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.0716

Gnomad AMR

AF:

0.0731

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0650

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0832

AC:

20532

AN:

246738

Hom.:

1036

AF XY:

0.0845

AC XY:

11320

AN XY:

134014

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0630

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0710

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0924

GnomAD4 exome

AF:

0.111

AC:

162647

AN:

1460618

Hom.:

10034

Cov.:

AF XY:

0.110

AC XY:

79981

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.0658

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0737

Gnomad4 FIN exome

AF:

0.0588

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0769

AC:

11712

AN:

152312

Hom.:

613

Cov.:

AF XY:

0.0741

AC XY:

5522

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.0730

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.0657

Gnomad4 FIN

AF:

0.0522

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0998

Alfa

AF:

0.103

Hom.:

1086

Bravo

AF:

0.0756

Asia WGS

AF:

0.0260

AC:

AN:

3476

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 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

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

1.7

DANN

Benign

0.74

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