rs3209030

Variant names:

• chr17-78427070-C-T
• rs3209030
• NM_173628.4:c.12627G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-78427070-C-T
• chr17-78427070-C-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.12627G>A​(p.Pro4209Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,591,330 control chromosomes in the GnomAD database, including 7,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (623 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6379 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.51
• Publications: 7 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=-0.65).
• BP6: Variant 17-78427070-C-T is Benign according to our data. Variant chr17-78427070-C-T is described in ClinVar as Benign. ClinVar VariationId is 402673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 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.12627G>A	p.Pro4209Pro	synonymous	Exon 78 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.12627G>A	p.Pro4209Pro	synonymous	Exon 78 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.5788G>A		non_coding_transcript_exon	Exon 32 of 35
	DNAH17	ENST00000586850.1	TSL:3	n.159G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13257 AN: 152094 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0919

GnomAD2 exomes AF: 0.0822 AC: 17452 AN: 212394 AF XY: 0.0853

Gnomad AFR exome AF: 0.0890

Gnomad AMR exome AF: 0.0509

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0317

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0931

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0912 AC: 131261 AN: 1439118 Hom.: 6379 Cov.: 36 AF XY: 0.0926 AC XY: 66122 AN XY: 713684

African (AFR) AF: 0.0947 AC: 3121 AN: 32944

American (AMR) AF: 0.0535 AC: 2208 AN: 41282

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2882 AN: 25642

East Asian (EAS) AF: 0.0282 AC: 1090 AN: 38600

South Asian (SAS) AF: 0.113 AC: 9348 AN: 82590

European-Finnish (FIN) AF: 0.0483 AC: 2497 AN: 51672

Middle Eastern (MID) AF: 0.157 AC: 905 AN: 5750

European-Non Finnish (NFE) AF: 0.0941 AC: 103609 AN: 1101024

Other (OTH) AF: 0.0940 AC: 5601 AN: 59614

GnomAD4 genome AF: 0.0871 AC: 13263 AN: 152212 Hom.: 623 Cov.: 32 AF XY: 0.0850 AC XY: 6322 AN XY: 74412

African (AFR) AF: 0.0935 AC: 3883 AN: 41540

American (AMR) AF: 0.0691 AC: 1056 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.0314 AC: 163 AN: 5190

South Asian (SAS) AF: 0.110 AC: 531 AN: 4826

European-Finnish (FIN) AF: 0.0424 AC: 450 AN: 10606

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6527 AN: 67982

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0938 Hom.: 372

Bravo AF: 0.0869

Asia WGS AF: 0.0790 AC: 279 AN: 3478

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	-0.65
CADD	Benign	2.9
DANN	Benign	0.90
PhyloP100		-2.5
Mutation Taster		=99/1	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: rs3209030; hg19: chr17-76423151; COSMIC: COSV53145967; COSMIC: COSV53145967;