dbSNP rs12941494: DNAH17:p.His3953Leu (chr17-78437816-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173628.4(DNAH17):c.11858A>T(p.His3953Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H3953Y) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

Publications

21 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15779674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.11858A>T	p.His3953Leu	missense	Exon 74 of 81	NP_775899.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.11858A>T	p.His3953Leu	missense	Exon 74 of 81	ENSP00000374490.6
DNAH17	ENST00000586052.5	TSL:5	n.4994A>T		non_coding_transcript_exon	Exon 28 of 35
DNAH17	ENST00000590227.5	TSL:2	n.1532A>T		non_coding_transcript_exon	Exon 6 of 13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726248

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111622

Other (OTH)

AF:

0.00

AC:

AN:

60330

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.23

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.55

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

PhyloP100

-0.14

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-9.8

REVEL

Benign

0.10

Sift

Uncertain

0.0080

Vest4

0.14

MVP

0.33

ClinPred

0.90

GERP RS

4.1

Varity_R

0.63

gMVP

0.51

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over