rs9894913

Variant names:

• chr17-78507445-G-A
• rs9894913
• NM_173628.4:c.4584+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78507445-G-A
• chr17-78507445-G-C
• chr17-78507445-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.4584+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,768 control chromosomes in the GnomAD database, including 74,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7721 hom., cov: 33)
  • Exomes 𝑓: 0.30 (66502 hom.)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.868
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-78507445-G-A is Benign according to our data. Variant chr17-78507445-G-A is described in ClinVar as Benign. ClinVar VariationId is 402688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.4584+13C>T		intron_variant	Intron 28 of 80	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.4584+13C>T		intron_variant	Intron 28 of 80	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000587177.1	n.636+13C>T		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47227 AN: 152020 Hom.: 7720 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.277 AC: 68968 AN: 248816 AF XY: 0.284

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.0732

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.298

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.297 AC: 434185 AN: 1460630 Hom.: 66502 Cov.: 40 AF XY: 0.299 AC XY: 217479 AN XY: 726376

African (AFR) AF: 0.383 AC: 12804 AN: 33464

American (AMR) AF: 0.192 AC: 8598 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 8534 AN: 26122

East Asian (EAS) AF: 0.0803 AC: 3183 AN: 39654

South Asian (SAS) AF: 0.366 AC: 31590 AN: 86232

European-Finnish (FIN) AF: 0.258 AC: 13758 AN: 53384

Middle Eastern (MID) AF: 0.296 AC: 1705 AN: 5766

European-Non Finnish (NFE) AF: 0.302 AC: 335903 AN: 1110974

Other (OTH) AF: 0.300 AC: 18110 AN: 60344

GnomAD4 genome AF: 0.311 AC: 47245 AN: 152138 Hom.: 7721 Cov.: 33 AF XY: 0.307 AC XY: 22805 AN XY: 74388

African (AFR) AF: 0.387 AC: 16054 AN: 41474

American (AMR) AF: 0.238 AC: 3642 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3470

East Asian (EAS) AF: 0.0811 AC: 420 AN: 5176

South Asian (SAS) AF: 0.356 AC: 1715 AN: 4822

European-Finnish (FIN) AF: 0.244 AC: 2581 AN: 10594

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20668 AN: 67992

Other (OTH) AF: 0.301 AC: 636 AN: 2112

Alfa AF: 0.303 Hom.: 23248

Bravo AF: 0.309

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.44
PhyloP100		-0.87
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: rs9894913; hg19: chr17-76503527; COSMIC: COSV67749911; COSMIC: COSV67749911;