rs72925845

Variant names:

• chr17-78443279-G-A
• rs72925845
• NM_173628.4:c.11528+1325C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173628.4(DNAH17):​c.11528+1325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,222 control chromosomes in the GnomAD database, including 616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.087 (616 hom., cov: 32)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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.11528+1325C>T		intron	N/A	NP_775899.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.11528+1325C>T		intron	N/A	ENSP00000374490.6
	DNAH17	ENST00000586052.5	TSL:5	n.4813+1325C>T		intron	N/A
	DNAH17	ENST00000590227.5	TSL:2	n.1202+1325C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13181 AN: 152104 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0866 AC: 13180 AN: 152222 Hom.: 616 Cov.: 32 AF XY: 0.0840 AC XY: 6249 AN XY: 74436

African (AFR) AF: 0.0519 AC: 2155 AN: 41562

American (AMR) AF: 0.0725 AC: 1109 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3472

East Asian (EAS) AF: 0.0520 AC: 269 AN: 5178

South Asian (SAS) AF: 0.0733 AC: 354 AN: 4828

European-Finnish (FIN) AF: 0.0694 AC: 736 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7645 AN: 67968

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.102 Hom.: 1130

Bravo AF: 0.0863

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.83
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72925845; hg19: chr17-76439361;