Variant 3-52370095-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015512.5(DNAH1):c.6139-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,613,830 control chromosomes in the GnomAD database, including 10,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 631 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10236 hom. )

Consequence

DNAH1
NM_015512.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.325

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 (BayesDel_noAF=-0.81).

BP6

Variant 3-52370095-G-A is Benign according to our data. Variant chr3-52370095-G-A is described in ClinVar as [Benign]. Clinvar id is 402600.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	Effect	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.6139-15G>A	intron_variant	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.6208-15G>A	intron_variant		XP_016861618.1
DNAH1	XM_017006130.2 link	c.6139-15G>A	intron_variant		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.6208-15G>A	intron_variant		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.6139-15G>A		intron_variant		1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.6400-15G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0822

AC:

12504

AN:

152170

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0658

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0851

AC:

21189

AN:

248960

Hom.:

1080

AF XY:

0.0861

AC XY:

11629

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0642

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0722

Gnomad FIN exome

AF:

0.0564

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.113

AC:

164725

AN:

1461542

Hom.:

10236

Cov.:

AF XY:

0.111

AC XY:

81007

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0371

Gnomad4 AMR exome

AF:

0.0672

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0751

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0821

AC:

12505

AN:

152288

Hom.:

631

Cov.:

AF XY:

0.0791

AC XY:

5888

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0752

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0665

Gnomad4 FIN

AF:

0.0527

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.100

Hom.:

157

Bravo

AF:

0.0812

Asia WGS

AF:

0.0280

AC:

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

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

-0.81

CADD

Benign

0.64

DANN

Benign

0.75

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