rs1057519568

Positions:

• chrX-107222767-CAGGTGGG-C

Variant summary

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

The NM_173494.2(DNAAF6):​c.357_363del​(p.Val120LeufsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: DNAAF6 NM_173494.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.24

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-CAGGTGGG-C is Pathogenic according to our data. Variant chrX-107222767-CAGGTGGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 375562.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF6	NM_173494.2	c.357_363del	p.Val120LeufsTer6	frameshift_variant	5/7	ENST00000372453.8
DNAAF6	NM_001169154.2	c.357_363del	p.Val120LeufsTer6	frameshift_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF6	ENST00000372453.8	c.357_363del	p.Val120LeufsTer6	frameshift_variant	5/7	1	NM_173494.2	P1
DNAAF6	ENST00000336387.4	c.357_363del	p.Val120LeufsTer6	frameshift_variant	5/7	5		P1
DNAAF6	ENST00000535523.6	c.357_363del	p.Val120LeufsTer6	frameshift_variant	6/8	5		P1
DNAAF6	ENST00000688816.1	c.332+3800_332+3806del		intron_variant

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519568; hg19: chrX-106465997;