rs11651537

Variant names:

• chr17-78532708-A-G
• rs11651537
• NM_173628.4:c.2888T>C
• DNAH17 p.Ile963Thr

Your query was ambiguous. Multiple possible variants found:

• chr17-78532708-A-G
• chr17-78532708-A-C
• chr17-78532708-A-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.2888T>C​(p.Ile963Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,590,510 control chromosomes in the GnomAD database, including 211,095 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 0.51 (19651 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191444 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.338
• Publications: 21 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]

RN7SL454P (HGNC:46470): (RNA, 7SL, cytoplasmic 454, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.5595555E-4).
• BP6: Variant 17-78532708-A-G is Benign according to our data. Variant chr17-78532708-A-G is described in ClinVar as Benign. ClinVar VariationId is 402697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 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.2888T>C	p.Ile963Thr	missense	Exon 20 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.2888T>C	p.Ile963Thr	missense	Exon 20 of 81	ENSP00000374490.6	Q9UFH2-1
	RN7SL454P	ENST00000492744.3	TSL:6	n.*105T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76780 AN: 151748 Hom.: 19642 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.481 AC: 104088 AN: 216402 AF XY: 0.485

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.425

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.529

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.514 AC: 740145 AN: 1438644 Hom.: 191444 Cov.: 48 AF XY: 0.513 AC XY: 365806 AN XY: 713286

African (AFR) AF: 0.483 AC: 15971 AN: 33094

American (AMR) AF: 0.383 AC: 16001 AN: 41784

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 13320 AN: 25518

East Asian (EAS) AF: 0.439 AC: 17171 AN: 39102

South Asian (SAS) AF: 0.434 AC: 35977 AN: 82940

European-Finnish (FIN) AF: 0.521 AC: 27078 AN: 51944

Middle Eastern (MID) AF: 0.542 AC: 3051 AN: 5626

European-Non Finnish (NFE) AF: 0.529 AC: 581011 AN: 1099062

Other (OTH) AF: 0.513 AC: 30565 AN: 59574

GnomAD4 genome AF: 0.506 AC: 76821 AN: 151866 Hom.: 19651 Cov.: 31 AF XY: 0.502 AC XY: 37239 AN XY: 74210

African (AFR) AF: 0.490 AC: 20267 AN: 41374

American (AMR) AF: 0.435 AC: 6635 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1773 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2218 AN: 5168

South Asian (SAS) AF: 0.422 AC: 2027 AN: 4808

European-Finnish (FIN) AF: 0.524 AC: 5531 AN: 10552

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36444 AN: 67934

Other (OTH) AF: 0.517 AC: 1086 AN: 2102

Alfa AF: 0.516 Hom.: 37421

Bravo AF: 0.499

Asia WGS AF: 0.429 AC: 1491 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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.9
DANN	Benign	0.60
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.34
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.062
Sift	Benign	0.65	T
Varity_R		0.062
gMVP		0.25
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11651537;

hg19: chr17-76528790;

COSMIC: COSV67758202;

COSMIC: COSV67758202;