Variant rs61733359 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_130810.4(DNAAF4):c.128A>G(p.Asn43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,610,242 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

DNAAF4
NM_130810.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4 links:

DNAAF4-CCPG1 (HGNC:):

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047905147).

BP6

Variant 15-55497855-T-C is Benign according to our data. Variant chr15-55497855-T-C is described in ClinVar as [Benign]. Clinvar id is 241831.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00422 (642/152254) while in subpopulation AFR AF= 0.0145 (601/41540). AF 95% confidence interval is 0.0135. There are 6 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAAF4	NM_130810.4 linkuse as main transcript	c.128A>G	p.Asn43Ser	missense_variant	3/10	ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1 linkuse as main transcript	n.383A>G		non_coding_transcript_exon_variant	2/16
DNAAF4	NM_001033560.2 linkuse as main transcript	c.128A>G	p.Asn43Ser	missense_variant	3/9
DNAAF4	NM_001033559.3 linkuse as main transcript	c.128A>G	p.Asn43Ser	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7 linkuse as main transcript	c.128A>G	p.Asn43Ser	missense_variant	3/10	1	NM_130810.4	P1	Q8WXU2-1

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

630

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00106

AC:

261

AN:

247346

Hom.:

AF XY:

0.000809

AC XY:

108

AN XY:

133550

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000396

AC:

577

AN:

1457988

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

226

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00422

AC:

642

AN:

152254

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00459

ESP6500AA

AF:

0.0135

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0014

.;.;T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.86

D;D;D;.

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.80

N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.64

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.65

T;T;T;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.37

B;B;B;B

Vest4

0.21

MVP

0.44

MPC

0.051

ClinPred

0.014

GERP RS

3.6

Varity_R

0.058

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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