NM_173628.4:c.12627G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173628.4(DNAH17):c.12627G>A(p.Pro4209Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,591,330 control chromosomes in the GnomAD database, including 7,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 623 hom., cov: 32)

Exomes 𝑓: 0.091 ( 6379 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.51

Publications

7 publications found

Variant links:

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

DNAH17 Gene-Disease associations (from GenCC):

spermatogenic failure 39
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAH17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 17-78427070-C-T is Benign according to our data. Variant chr17-78427070-C-T is described in ClinVar as [Benign]. Clinvar id is 402673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.12627G>A	p.Pro4209Pro	synonymous_variant	Exon 78 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1
DNAH17	XM_011525416.3 link	c.12639G>A	p.Pro4213Pro	synonymous_variant	Exon 78 of 81		XP_011523718.1
DNAH17	XM_024451013.2 link	c.12495G>A	p.Pro4165Pro	synonymous_variant	Exon 77 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.12627G>A	p.Pro4209Pro	synonymous_variant	Exon 78 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13257

AN:

152094

Hom.:

622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0936

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0691

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0313

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0424

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0960

Gnomad OTH

AF:

0.0919

GnomAD2 exomes

AF:

0.0822

AC:

17452

AN:

212394

AF XY:

0.0853

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.0509

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.0317

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0931

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0912

AC:

131261

AN:

1439118

Hom.:

6379

Cov.:

AF XY:

0.0926

AC XY:

66122

AN XY:

713684

show subpopulations

African (AFR)

AF:

0.0947

AC:

3121

AN:

32944

American (AMR)

AF:

0.0535

AC:

2208

AN:

41282

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2882

AN:

25642

East Asian (EAS)

AF:

0.0282

AC:

1090

AN:

38600

South Asian (SAS)

AF:

0.113

AC:

9348

AN:

82590

European-Finnish (FIN)

AF:

0.0483

AC:

2497

AN:

51672

Middle Eastern (MID)

AF:

0.157

AC:

905

AN:

5750

European-Non Finnish (NFE)

AF:

0.0941

AC:

103609

AN:

1101024

Other (OTH)

AF:

0.0940

AC:

5601

AN:

59614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7042

14084

21125

28167

35209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0871

AC:

13263

AN:

152212

Hom.:

623

Cov.:

AF XY:

0.0850

AC XY:

6322

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0935

AC:

3883

AN:

41540

American (AMR)

AF:

0.0691

AC:

1056

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

380

AN:

3470

East Asian (EAS)

AF:

0.0314

AC:

163

AN:

5190

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4826

European-Finnish (FIN)

AF:

0.0424

AC:

450

AN:

10606

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0960

AC:

6527

AN:

67982

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

661

1322

1983

2644

3305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0938

Hom.:

372

Bravo

AF:

0.0869

Asia WGS

AF:

0.0790

AC:

279

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

Aug 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

DNAH17-related disorder

Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.9

(source)

DANN

Benign

0.90

PhyloP100

-2.5

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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NM_173628.4:c.12627G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over