rs36119275

Variant names:

• chr17-78425386-A-G
• rs36119275
• NM_173628.4:c.13101T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-78425386-A-G
• chr17-78425386-A-C
• chr17-78425386-A-T

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.13101T>C​(p.Pro4367Pro) 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 1,613,646 control chromosomes in the GnomAD database, including 23,050 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 (20604 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.23
• Publications: 15 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=-0.88).
• BP6: Variant 17-78425386-A-G is Benign according to our data. Variant chr17-78425386-A-G is described in ClinVar as Benign. ClinVar VariationId is 402671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 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.13101T>C	p.Pro4367Pro	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.13101T>C	p.Pro4367Pro	synonymous	Exon 80 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.6262T>C		non_coding_transcript_exon	Exon 34 of 35
	DNAH17	ENST00000590227.5	TSL:2	n.2775T>C		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26294 AN: 151970 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: 0.153

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.150 AC: 37697 AN: 251048 AF XY: 0.154

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0906

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0353

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.163 AC: 238709 AN: 1461558 Hom.: 20604 Cov.: 33 AF XY: 0.163 AC XY: 118617 AN XY: 727064

African (AFR) AF: 0.235 AC: 7863 AN: 33478

American (AMR) AF: 0.0931 AC: 4164 AN: 44724

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

East Asian (EAS) AF: 0.0217 AC: 860 AN: 39700

South Asian (SAS) AF: 0.164 AC: 14108 AN: 86250

European-Finnish (FIN) AF: 0.113 AC: 6057 AN: 53384

Middle Eastern (MID) AF: 0.204 AC: 1178 AN: 5768

European-Non Finnish (NFE) AF: 0.170 AC: 188583 AN: 1111752

Other (OTH) AF: 0.163 AC: 9816 AN: 60370

GnomAD4 genome AF: 0.173 AC: 26314 AN: 152088 Hom.: 2446 Cov.: 32 AF XY: 0.168 AC XY: 12521 AN XY: 74350

African (AFR) AF: 0.230 AC: 9520 AN: 41436

American (AMR) AF: 0.130 AC: 1986 AN: 15280

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

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

South Asian (SAS) AF: 0.153 AC: 736 AN: 4820

European-Finnish (FIN) AF: 0.111 AC: 1181 AN: 10604

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

European-Non Finnish (NFE) AF: 0.167 AC: 11344 AN: 67978

Other (OTH) AF: 0.177 AC: 375 AN: 2116

Alfa AF: 0.178 Hom.: 1638

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	-0.88
CADD	Benign	0.55
DANN	Benign	0.54
PhyloP100		-2.2
Mutation Taster		=86/14	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: rs36119275; hg19: chr17-76421467; COSMIC: COSV53147123; COSMIC: COSV53147123;