rs930571

Variant names:

• chr17-78502610-C-T
• rs930571
• NM_173628.4:c.5171G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-78502610-C-T
• chr17-78502610-C-A
• chr17-78502610-C-G

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.5171G>A​(p.Arg1724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,612,524 control chromosomes in the GnomAD database, including 568,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58178 hom., cov: 32)
  • Exomes 𝑓: 0.83 (509829 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.91
• Publications: 23 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-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.9313097E-7).
• BP6: Variant 17-78502610-C-T is Benign according to our data. Variant chr17-78502610-C-T is described in ClinVar as Benign. ClinVar VariationId is 402687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.5171G>A	p.Arg1724Lys	missense	Exon 33 of 81	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.4717C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.5171G>A	p.Arg1724Lys	missense	Exon 33 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17-AS1	ENST00000598378.2	TSL:2	n.4151C>T		non_coding_transcript_exon	Exon 2 of 2
	DNAH17	ENST00000587177.1	TSL:5	n.1135-73G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132484 AN: 152158 Hom.: 58116 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.877

GnomAD2 exomes AF: 0.865 AC: 213738 AN: 247090 AF XY: 0.862

Gnomad AFR exome AF: 0.972

Gnomad AMR exome AF: 0.919

Gnomad ASJ exome AF: 0.870

Gnomad EAS exome AF: 0.977

Gnomad FIN exome AF: 0.810

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.834 AC: 1218005 AN: 1460248 Hom.: 509829 Cov.: 47 AF XY: 0.835 AC XY: 606759 AN XY: 726394

African (AFR) AF: 0.975 AC: 32615 AN: 33446

American (AMR) AF: 0.915 AC: 40715 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 22716 AN: 26122

East Asian (EAS) AF: 0.988 AC: 39199 AN: 39686

South Asian (SAS) AF: 0.925 AC: 79698 AN: 86140

European-Finnish (FIN) AF: 0.811 AC: 42953 AN: 52956

Middle Eastern (MID) AF: 0.862 AC: 4972 AN: 5766

European-Non Finnish (NFE) AF: 0.813 AC: 903644 AN: 1111320

Other (OTH) AF: 0.853 AC: 51493 AN: 60336

GnomAD4 genome AF: 0.871 AC: 132605 AN: 152276 Hom.: 58178 Cov.: 32 AF XY: 0.873 AC XY: 65030 AN XY: 74460

African (AFR) AF: 0.967 AC: 40217 AN: 41568

American (AMR) AF: 0.880 AC: 13450 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3470

East Asian (EAS) AF: 0.978 AC: 5065 AN: 5180

South Asian (SAS) AF: 0.932 AC: 4496 AN: 4826

European-Finnish (FIN) AF: 0.810 AC: 8596 AN: 10606

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54879 AN: 68014

Other (OTH) AF: 0.879 AC: 1858 AN: 2114

Alfa AF: 0.842 Hom.: 101997

Bravo AF: 0.881

TwinsUK AF: 0.817 AC: 3029

ALSPAC AF: 0.814 AC: 3139

ESP6500AA AF: 0.971 AC: 3895

ESP6500EA AF: 0.812 AC: 6854

ExAC AF: 0.864 AC: 104442

Asia WGS AF: 0.965 AC: 3357 AN: 3478

EpiCase AF: 0.809

EpiControl AF: 0.814

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	0.076
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.46
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	6.9e-7	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.9
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.054
Vest4		0.024
ClinPred		0.010	T
GERP RS		3.3
Varity_R		0.060
gMVP		0.22
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: rs930571; hg19: chr17-76498692; COSMIC: COSV107502939; COSMIC: COSV107502939;