rs1057519569

Positions:

• chrX-107222767-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_173494.2(DNAAF6):​c.355C>T​(p.Gln119*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: DNAAF6 NM_173494.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.541

Genes affected

DNAAF6 (HGNC:28570): (dynein axonemal assembly factor 6) Enables dynein intermediate chain binding activity. Involved in flagellated sperm motility; inner dynein arm assembly; and outer dynein arm assembly. Located in trans-Golgi network. Implicated in primary ciliary dyskinesia 36. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-107222767-C-T is Pathogenic according to our data. Variant chrX-107222767-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375563.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF6	NM_173494.2	c.355C>T	p.Gln119*	stop_gained	5/7	ENST00000372453.8	NP_775765.1
DNAAF6	NM_001169154.2	c.355C>T	p.Gln119*	stop_gained	6/8		NP_001162625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF6	ENST00000372453.8	c.355C>T	p.Gln119*	stop_gained	5/7	1	NM_173494.2	ENSP00000361531.3
DNAAF6	ENST00000336387.4	c.355C>T	p.Gln119*	stop_gained	5/7	5		ENSP00000337757.4
DNAAF6	ENST00000535523.6	c.355C>T	p.Gln119*	stop_gained	6/8	5		ENSP00000441930.1
DNAAF6	ENST00000688816.1	c.332+3798C>T		intron_variant				ENSP00000508655.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ciliary dyskinesia, primary, 36, X-linked Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	33
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.71	D
Vest4		0.39
GERP RS		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.40		Position offset: -22

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1057519569; hg19: chrX-106465997;