17-78425362-G-A

Variant names:

• chr17-78425362-G-A
• rs1134541
• NM_173628.4:c.13125C>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.13125C>T​(p.Tyr4375Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,613,696 control chromosomes in the GnomAD database, including 8,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1087 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6924 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.540
• 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]

PGS1 (HGNC:30029): (phosphatidylglycerophosphate synthase 1) Predicted to enable CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity and calcium ion binding activity. Predicted to be involved in cardiolipin biosynthetic process and diacylglycerol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-78425362-G-A is Benign according to our data. Variant chr17-78425362-G-A is described in ClinVar as Benign. ClinVar VariationId is 402669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 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.13125C>T	p.Tyr4375Tyr	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.13125C>T	p.Tyr4375Tyr	synonymous	Exon 80 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.6286C>T		non_coding_transcript_exon	Exon 34 of 35
	DNAH17	ENST00000590227.5	TSL:2	n.2799C>T		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16846 AN: 152100 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.0876 AC: 21978 AN: 250864 AF XY: 0.0892

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.0274

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0914

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0935 AC: 136608 AN: 1461478 Hom.: 6924 Cov.: 31 AF XY: 0.0946 AC XY: 68801 AN XY: 727040

African (AFR) AF: 0.179 AC: 6003 AN: 33476

American (AMR) AF: 0.0577 AC: 2581 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3034 AN: 26132

East Asian (EAS) AF: 0.0261 AC: 1035 AN: 39694

South Asian (SAS) AF: 0.113 AC: 9752 AN: 86244

European-Finnish (FIN) AF: 0.0487 AC: 2598 AN: 53346

Middle Eastern (MID) AF: 0.161 AC: 927 AN: 5768

European-Non Finnish (NFE) AF: 0.0942 AC: 104707 AN: 1111734

Other (OTH) AF: 0.0989 AC: 5971 AN: 60366

GnomAD4 genome AF: 0.111 AC: 16859 AN: 152218 Hom.: 1087 Cov.: 33 AF XY: 0.107 AC XY: 7926 AN XY: 74408

African (AFR) AF: 0.174 AC: 7236 AN: 41520

American (AMR) AF: 0.0805 AC: 1230 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3470

East Asian (EAS) AF: 0.0290 AC: 150 AN: 5180

South Asian (SAS) AF: 0.109 AC: 528 AN: 4826

European-Finnish (FIN) AF: 0.0426 AC: 452 AN: 10608

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6549 AN: 68010

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.103 Hom.: 455

Bravo AF: 0.114

Asia WGS AF: 0.0810 AC: 286 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	-0.49
CADD	Benign	0.29
DANN	Benign	0.88
PhyloP100		-0.54
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

Other links and lift over

dbSNP: rs1134541; hg19: chr17-76421443; COSMIC: COSV53149078; COSMIC: COSV53149078;