Variant 3-52358734-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015512.5(DNAH1):c.4263C>T(p.Pro1421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,612,128 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 65 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.221

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-52358734-C-T is Benign according to our data. Variant chr3-52358734-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.221 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00373 (568/152276) while in subpopulation SAS AF= 0.023 (111/4824). AF 95% confidence interval is 0.0195. There are 4 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAH1	NM_015512.5 linkuse as main transcript	c.4263C>T	p.Pro1421=	synonymous_variant	25/78	ENST00000420323.7
DNAH1	XM_017006129.2 linkuse as main transcript	c.4263C>T	p.Pro1421=	synonymous_variant	26/80
DNAH1	XM_017006130.2 linkuse as main transcript	c.4263C>T	p.Pro1421=	synonymous_variant	26/79
DNAH1	XM_017006131.2 linkuse as main transcript	c.4263C>T	p.Pro1421=	synonymous_variant	26/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.4263C>T	p.Pro1421=	synonymous_variant	25/78	1	NM_015512.5	P1	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.4524C>T		non_coding_transcript_exon_variant	25/77	2

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00444

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00561

AC:

1386

AN:

246870

Hom.:

AF XY:

0.00667

AC XY:

897

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.000849

Gnomad AMR exome

AF:

0.00233

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00358

Gnomad SAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.00577

AC:

8425

AN:

1459852

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

4586

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00376

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00510

Gnomad4 OTH exome

AF:

0.00562

GnomAD4 genome

AF:

0.00373

AC:

568

AN:

152276

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00445

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00471

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.00290

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00505

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 25, 2023	- -
Likely 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

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.6

DANN

Benign

0.62

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