rs1134541

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.13125C>T(p.Tyr4375Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,613,696 control chromosomes in the GnomAD database, including 8,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1087 hom., cov: 33)

Exomes 𝑓: 0.093 ( 6924 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.540

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 links:

PGS1 (HGNC:30029): (phosphatidylglycerophosphate synthase 1) Predicted to enable CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity and calcium ion binding activity. Predicted to be involved in cardiolipin biosynthetic process and diacylglycerol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

PGS1 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=-0.49).

BP6

Variant 17-78425362-G-A is Benign according to our data. Variant chr17-78425362-G-A is described in ClinVar as [Benign]. Clinvar id is 402669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.13125C>T	p.Tyr4375Tyr	synonymous_variant	Exon 80 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1
DNAH17	XM_011525416.3 link	c.13137C>T	p.Tyr4379Tyr	synonymous_variant	Exon 80 of 81		XP_011523718.1
DNAH17	XM_024451013.2 link	c.12993C>T	p.Tyr4331Tyr	synonymous_variant	Exon 79 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.13125C>T	p.Tyr4375Tyr	synonymous_variant	Exon 80 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16846

AN:

152100

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0805

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0289

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0426

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0963

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.0876

AC:

21978

AN:

250864

AF XY:

0.0892

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0545

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.0274

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0914

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0935

AC:

136608

AN:

1461478

Hom.:

6924

Cov.:

AF XY:

0.0946

AC XY:

68801

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.179

AC:

6003

AN:

33476

American (AMR)

AF:

0.0577

AC:

2581

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

3034

AN:

26132

East Asian (EAS)

AF:

0.0261

AC:

1035

AN:

39694

South Asian (SAS)

AF:

0.113

AC:

9752

AN:

86244

European-Finnish (FIN)

AF:

0.0487

AC:

2598

AN:

53346

Middle Eastern (MID)

AF:

0.161

AC:

927

AN:

5768

European-Non Finnish (NFE)

AF:

0.0942

AC:

104707

AN:

1111734

Other (OTH)

AF:

0.0989

AC:

5971

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6085

12169

18254

24338

30423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16859

AN:

152218

Hom.:

1087

Cov.:

AF XY:

0.107

AC XY:

7926

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.174

AC:

7236

AN:

41520

American (AMR)

AF:

0.0805

AC:

1230

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3470

East Asian (EAS)

AF:

0.0290

AC:

150

AN:

5180

South Asian (SAS)

AF:

0.109

AC:

528

AN:

4826

European-Finnish (FIN)

AF:

0.0426

AC:

452

AN:

10608

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0963

AC:

6549

AN:

68010

Other (OTH)

AF:

0.110

AC:

232

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

760

1521

2281

3042

3802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.103

Hom.:

455

Bravo

AF:

0.114

Asia WGS

AF:

0.0810

AC:

286

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

May 04, 2021

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

-0.49

CADD

Benign

0.29

(source)

DANN

Benign

0.88

PhyloP100

-0.54

Mutation Taster

=100/0

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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rs1134541

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