rs61741523

Variant names:

• chr17-78529677-G-C
• rs61741523
• NM_173628.4:c.3302C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-78529677-G-C
• chr17-78529677-G-A
• chr17-78529677-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.3302C>G​(p.Ala1101Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,568 control chromosomes in the GnomAD database, including 27,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1858 hom., cov: 31)
  • Exomes 𝑓: 0.18 (25358 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.526
• Publications: 17 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 (MetaRNN=0.004291922).
• BP6: Variant 17-78529677-G-C is Benign according to our data. Variant chr17-78529677-G-C is described in ClinVar as Benign. ClinVar VariationId is 402695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 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.3302C>G	p.Ala1101Gly	missense	Exon 22 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.3302C>G	p.Ala1101Gly	missense	Exon 22 of 81	ENSP00000374490.6	Q9UFH2-1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21040 AN: 152000 Hom.: 1857 Cov.: 31

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.168 AC: 41880 AN: 249026 AF XY: 0.171

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.182 AC: 265621 AN: 1461450 Hom.: 25358 Cov.: 44 AF XY: 0.182 AC XY: 132509 AN XY: 727014

African (AFR) AF: 0.0336 AC: 1125 AN: 33480

American (AMR) AF: 0.214 AC: 9575 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3370 AN: 26136

East Asian (EAS) AF: 0.106 AC: 4214 AN: 39696

South Asian (SAS) AF: 0.223 AC: 19265 AN: 86252

European-Finnish (FIN) AF: 0.107 AC: 5739 AN: 53386

Middle Eastern (MID) AF: 0.133 AC: 766 AN: 5766

European-Non Finnish (NFE) AF: 0.190 AC: 211326 AN: 1111658

Other (OTH) AF: 0.170 AC: 10241 AN: 60364

GnomAD4 genome AF: 0.138 AC: 21049 AN: 152118 Hom.: 1858 Cov.: 31 AF XY: 0.137 AC XY: 10215 AN XY: 74360

African (AFR) AF: 0.0420 AC: 1745 AN: 41534

American (AMR) AF: 0.189 AC: 2893 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.115 AC: 592 AN: 5168

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4814

European-Finnish (FIN) AF: 0.0988 AC: 1045 AN: 10576

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12702 AN: 67964

Other (OTH) AF: 0.157 AC: 330 AN: 2102

Alfa AF: 0.166 Hom.: 1830

Bravo AF: 0.141

TwinsUK AF: 0.198 AC: 736

ALSPAC AF: 0.208 AC: 803

ESP6500AA AF: 0.0421 AC: 164

ESP6500EA AF: 0.191 AC: 1576

ExAC AF: 0.165 AC: 19998

Asia WGS AF: 0.154 AC: 532 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.188

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.5
DANN	Benign	0.80
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.53
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.014
Sift	Benign	0.37	T
Vest4		0.044
ClinPred		0.00018	T
GERP RS		1.4
Varity_R		0.032
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61741523; hg19: chr17-76525759; COSMIC: COSV67751204; COSMIC: COSV67751204;