rs35422926

Variant names:

• chr17-78425383-C-T
• rs35422926
• NM_173628.4:c.13104G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173628.4(DNAH17):​c.13104G>A​(p.Pro4368Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,606 control chromosomes in the GnomAD database, including 23,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2446 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20603 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.942
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-78425383-C-T is Benign according to our data. Variant chr17-78425383-C-T is described in ClinVar as Benign. ClinVar VariationId is 402670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.942 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.13104G>A	p.Pro4368Pro	synonymous	Exon 80 of 81	NP_775899.3	Q9UFH2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13104G>A	p.Pro4368Pro	synonymous	Exon 80 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.6265G>A		non_coding_transcript_exon	Exon 34 of 35
	DNAH17	ENST00000590227.5	TSL:2	n.2778G>A		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26288 AN: 151974 Hom.: 2443 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.150 AC: 37695 AN: 251026 AF XY: 0.154

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0905

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0352

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.163 AC: 238682 AN: 1461514 Hom.: 20603 Cov.: 33 AF XY: 0.163 AC XY: 118595 AN XY: 727036

African (AFR) AF: 0.235 AC: 7860 AN: 33478

American (AMR) AF: 0.0931 AC: 4162 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 6080 AN: 26132

East Asian (EAS) AF: 0.0217 AC: 861 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14097 AN: 86250

European-Finnish (FIN) AF: 0.113 AC: 6055 AN: 53374

Middle Eastern (MID) AF: 0.204 AC: 1178 AN: 5766

European-Non Finnish (NFE) AF: 0.170 AC: 188572 AN: 1111726

Other (OTH) AF: 0.163 AC: 9817 AN: 60368

GnomAD4 genome AF: 0.173 AC: 26308 AN: 152092 Hom.: 2446 Cov.: 32 AF XY: 0.168 AC XY: 12512 AN XY: 74346

African (AFR) AF: 0.230 AC: 9517 AN: 41440

American (AMR) AF: 0.130 AC: 1985 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5182

South Asian (SAS) AF: 0.152 AC: 732 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1182 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11345 AN: 67986

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.181 Hom.: 1137

Bravo AF: 0.178

Asia WGS AF: 0.0790 AC: 274 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.176

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH17-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.88
DANN	Benign	0.92
PhyloP100		-0.94
Mutation Taster		=90/10	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: rs35422926; hg19: chr17-76421464; COSMIC: COSV53145271; COSMIC: COSV53145271;