Variant X-107216580-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173494.2(DNAAF6):c.154-91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 580,014 control chromosomes in the GnomAD database, including 18,952 homozygotes. There are 37,996 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 8020 hom., 11645 hem., cov: 22)

Exomes 𝑓: 0.22 ( 10932 hom. 26351 hem. )

Consequence

DNAAF6
NM_173494.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.545

Variant links:

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]

DNAAF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-107216580-T-G is Benign according to our data. Variant chrX-107216580-T-G is described in ClinVar as [Benign]. Clinvar id is 1227861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF6	NM_173494.2 linkuse as main transcript	c.154-91T>G		intron_variant		ENST00000372453.8	NP_775765.1
DNAAF6	NM_001169154.2 linkuse as main transcript	c.154-91T>G		intron_variant			NP_001162625.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DNAAF6	ENST00000372453.8 linkuse as main transcript	c.154-91T>G	intron_variant	1	NM_173494.2	ENSP00000361531.3	Q9NQM4
DNAAF6	ENST00000336387.4 linkuse as main transcript	c.154-91T>G	intron_variant	5		ENSP00000337757.4	Q9NQM4
DNAAF6	ENST00000535523.6 linkuse as main transcript	c.154-91T>G	intron_variant	5		ENSP00000441930.1	Q9NQM4
DNAAF6	ENST00000688816.1 linkuse as main transcript	c.154-91T>G	intron_variant			ENSP00000508655.1	A0A8I5QJ82

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

40579

AN:

110759

Hom.:

8019

Cov.:

AF XY:

0.351

AC XY:

11601

AN XY:

33011

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.319

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.217

AC:

101915

AN:

469199

Hom.:

10932

AF XY:

0.233

AC XY:

26351

AN XY:

112857

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.367

AC:

40622

AN:

110815

Hom.:

8020

Cov.:

AF XY:

0.352

AC XY:

11645

AN XY:

33077

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.357

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.116

Hom.:

644

Bravo

AF:

0.410

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.43

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over