rs61733359

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 14/20 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Publications

3 publications found

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:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 241831.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 = 0.00422 (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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 10	ENST00000321149.7	NP_570722.2	Q8WXU2-1
DNAAF4	NM_001033560.2 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 9		NP_001028732.1	Q8WXU2-2A0A0S2Z5Z4
DNAAF4	NM_001033559.3 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 9		NP_001028731.1	Q8WXU2-3
DNAAF4-CCPG1	NR_037923.1 link	n.383A>G		non_coding_transcript_exon_variant	Exon 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 link	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 10	1	NM_130810.4	ENSP00000323275.3		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

GnomAD2 exomes

AF:

0.00106

AC:

261

AN:

247346

AF XY:

0.000809

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 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

African (AFR)

AF:

0.0130

AC:

434

AN:

33288

American (AMR)

AF:

0.00107

AC:

AN:

43914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.000101

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000589

AC:

AN:

84836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1110868

Other (OTH)

AF:

0.00116

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00422

AC:

642

AN:

152254

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0145

AC:

601

AN:

41540

American (AMR)

AF:

0.00203

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00252

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

1.6

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

PromoterAI

0.093

Neutral

(source)

Varity_R

0.058

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over