Variant 3-52392856-G-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.10305G>A(p.Thr3435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,597,196 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 64 hom., cov: 29)

Exomes 𝑓: 0.0019 ( 66 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.32

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=-0.43).

BP6

Variant 3-52392856-G-A is Benign according to our data. Variant chr3-52392856-G-A is described in ClinVar as [Benign]. Clinvar id is 478377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAH1	NM_015512.5 linkuse as main transcript	c.10305G>A	p.Thr3435=	synonymous_variant	65/78	ENST00000420323.7
DNAH1	XM_017006129.2 linkuse as main transcript	c.10374G>A	p.Thr3458=	synonymous_variant	67/80
DNAH1	XM_017006130.2 linkuse as main transcript	c.10305G>A	p.Thr3435=	synonymous_variant	66/79
DNAH1	XM_017006131.2 linkuse as main transcript	c.10248G>A	p.Thr3416=	synonymous_variant	66/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.10305G>A	p.Thr3435=	synonymous_variant	65/78	1	NM_015512.5	P1	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.10762G>A		non_coding_transcript_exon_variant	64/77	2
DNAH1	ENST00000488988.5 linkuse as main transcript	n.2091G>A		non_coding_transcript_exon_variant	12/25	2
DNAH1	ENST00000490713.5 linkuse as main transcript	c.1005G>A	p.Thr335=	synonymous_variant, NMD_transcript_variant	8/20	5

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2205

AN:

143144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0544

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000439

Gnomad FIN

AF:

0.000226

Gnomad MID

AF:

0.00680

Gnomad NFE

AF:

0.000703

Gnomad OTH

AF:

0.0107

GnomAD3 exomes

AF:

0.00391

AC:

969

AN:

247530

Hom.:

AF XY:

0.00282

AC XY:

379

AN XY:

134388

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000655

Gnomad OTH exome

AF:

0.00282

GnomAD4 exome

AF:

0.00189

AC:

2742

AN:

1453972

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1190

AN XY:

721488

show subpopulations

Gnomad4 AFR exome

AF:

0.0564

Gnomad4 AMR exome

AF:

0.00202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.000320

Gnomad4 NFE exome

AF:

0.000427

Gnomad4 OTH exome

AF:

0.00390

GnomAD4 genome

AF:

0.0154

AC:

2211

AN:

143224

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1021

AN XY:

68876

show subpopulations

Gnomad4 AFR

AF:

0.0544

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000441

Gnomad4 FIN

AF:

0.000226

Gnomad4 NFE

AF:

0.000703

Gnomad4 OTH

AF:

0.0106

Alfa

AF:

0.00622

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000830

ClinVar

Significance: 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	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2020	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.8

DANN

Benign

0.72

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