X-107212690-G-C

Position:

• chrX-107212690-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173494.2(DNAAF6):​c.-3-183G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 111,432 control chromosomes in the GnomAD database, including 67 homozygotes. There are 578 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.019 (67 hom., 578 hem., cov: 23)
• Consequence: DNAAF6 NM_173494.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.490

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-107212690-G-C is Benign according to our data. Variant chrX-107212690-G-C is described in ClinVar as [Benign]. Clinvar id is 1232186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF6	NM_173494.2	c.-3-183G>C		intron_variant		ENST00000372453.8	NP_775765.1
DNAAF6	NM_001169154.2	c.-3-183G>C		intron_variant			NP_001162625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF6	ENST00000372453.8	c.-3-183G>C		intron_variant		1	NM_173494.2	ENSP00000361531.3
DNAAF6	ENST00000336387.4	c.-3-183G>C		intron_variant		5		ENSP00000337757.4
DNAAF6	ENST00000535523.6	c.-3-183G>C		intron_variant		5		ENSP00000441930.1
DNAAF6	ENST00000688816.1	c.-3-183G>C		intron_variant				ENSP00000508655.1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2138 AN: 111381 Hom.: 66 Cov.: 23 AF XY: 0.0171 AC XY: 575 AN XY: 33577

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00196

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0192 AC: 2145 AN: 111432 Hom.: 67 Cov.: 23 AF XY: 0.0172 AC XY: 578 AN XY: 33638

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.00823

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00196

Gnomad4 SAS AF: 0.00191

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0146

Alfa AF: 0.0161 Hom.: 52

Bravo AF: 0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.53

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: rs143167222; hg19: chrX-106455920;