7-756843-T-G

Position:

chr7-756843-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017802.4(DNAAF5):c.1319T>G(p.Ile440Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,613,996 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 11 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.46

Variant links:

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 links:

DNAAF5 (HGNC:):

DNAAF5 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 (MetaRNN=0.010664344).

BP6

Variant 7-756843-T-G is Benign according to our data. Variant chr7-756843-T-G is described in ClinVar as [Benign]. Clinvar id is 454850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0047 (716/152306) while in subpopulation AFR AF= 0.0163 (676/41560). AF 95% confidence interval is 0.0153. There are 4 homozygotes in gnomad4. There are 350 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF5	NM_017802.4 linkuse as main transcript	c.1319T>G	p.Ile440Ser	missense_variant	6/13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 linkuse as main transcript	c.1319T>G	p.Ile440Ser	missense_variant	6/12		XP_024302581.1
DNAAF5	NR_075098.2 linkuse as main transcript	n.1279T>G		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11 linkuse as main transcript	c.1319T>G	p.Ile440Ser	missense_variant	6/13	1	NM_017802.4	ENSP00000297440.6		Q86Y56-1
DNAAF5	ENST00000440747.5 linkuse as main transcript	c.722T>G	p.Ile241Ser	missense_variant	6/13	2		ENSP00000403165.1		H0Y650

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

716

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00135

AC:

339

AN:

251384

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000561

AC:

820

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000505

AC XY:

367

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00470

AC:

716

AN:

152306

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

350

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000909

Hom.:

Bravo

AF:

0.00519

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00161

AC:

196

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 08, 2016	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.086

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.50

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.86

MVP

0.32

MPC

0.52

ClinPred

0.034

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

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