Variant chr3-52364681-C-T 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.5288C>T(p.Ser1763Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0036 in 1,613,932 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1763S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 77 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 102 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.04

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=0.0058948994).

BP6

Variant 3-52364681-C-T is Benign according to our data. Variant chr3-52364681-C-T is described in ClinVar as [Benign]. Clinvar id is 478459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAH1	NM_015512.5 linkuse as main transcript	c.5288C>T	p.Ser1763Leu	missense_variant	33/78	ENST00000420323.7
DNAH1	XM_017006129.2 linkuse as main transcript	c.5288C>T	p.Ser1763Leu	missense_variant	34/80
DNAH1	XM_017006130.2 linkuse as main transcript	c.5288C>T	p.Ser1763Leu	missense_variant	34/79
DNAH1	XM_017006131.2 linkuse as main transcript	c.5288C>T	p.Ser1763Leu	missense_variant	34/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.5288C>T	p.Ser1763Leu	missense_variant	33/78	1	NM_015512.5	P1	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.5549C>T		non_coding_transcript_exon_variant	33/77	2

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2825

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00484

AC:

1206

AN:

249056

Hom.:

AF XY:

0.00395

AC XY:

534

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.0688

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00204

AC:

2976

AN:

1461654

Hom.:

102

Cov.:

AF XY:

0.00177

AC XY:

1286

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0709

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.00446

GnomAD4 genome

AF:

0.0186

AC:

2829

AN:

152278

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1343

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.0223

ESP6500AA

AF:

0.0562

AC:

227

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00580

AC:

701

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 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

0.16

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.17

Sift

Benign

0.067

Sift4G

Uncertain

0.0070

Vest4

0.64

MVP

0.48

MPC

0.34

ClinPred

0.026

GERP RS

4.0

gMVP

0.59

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