rs1134541

Variant names:

• chr17-78425362-G-A
• rs1134541
• NM_173628.4:c.13125C>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13125C>T	p.Tyr4375Tyr	synonymous_variant	Exon 80 of 81	ENST00000389840.7	NP_775899.3
DNAH17	XM_011525416.3	c.13137C>T	p.Tyr4379Tyr	synonymous_variant	Exon 80 of 81		XP_011523718.1
DNAH17	XM_024451013.2	c.12993C>T	p.Tyr4331Tyr	synonymous_variant	Exon 79 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.13125C>T	p.Tyr4375Tyr	synonymous_variant	Exon 80 of 81	5	NM_173628.4	ENSP00000374490.6

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

GnomAD3 exomes AF: 0.0876 AC: 21978 AN: 250864 Hom.: 1186 AF XY: 0.0892 AC XY: 12096 AN XY: 135586

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 SAS exome AF: 0.114

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

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.0261

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0487

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.0989

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0805

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0426

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.110

Alfa AF: 0.103 Hom.: 444

Bravo AF: 0.114

Asia WGS AF: 0.0810 AC: 286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH17-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.29
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

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