rs199564997

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001033560.2(DNAAF4):c.1090C>T(p.Pro364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,580,710 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

DNAAF4
NM_001033560.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.698

Publications

2 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:

PIERCE2 (HGNC:44654): (piercer of microtubule wall 2)

PIERCE2 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055252016).

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIERCE2	NM_001198784.2	MANE Select	c.19-132G>A		intron	N/A	NP_001185713.1	H3BRN8
DNAAF4	NM_001033560.2		c.1090C>T	p.Pro364Ser	missense	Exon 9 of 9	NP_001028732.1	Q8WXU2-2
DNAAF4-CCPG1	NR_037923.1		n.1408+14406C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF4	ENST00000448430.6	TSL:1	c.1090C>T	p.Pro364Ser	missense	Exon 8 of 8	ENSP00000403412.2	Q8WXU2-2
PIERCE2	ENST00000569691.2	TSL:1 MANE Select	c.19-132G>A		intron	N/A	ENSP00000456337.1	H3BRN8
PIERCE2	ENST00000570794.2	TSL:3	c.81-132G>A		intron	N/A	ENSP00000516647.1	A0A9L9PYH9

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000223

AC:

AN:

220140

AF XY:

0.000218

show subpopulations

Gnomad AFR exome

AF:

0.0000637

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00349

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000144

AC:

205

AN:

1428522

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

123

AN XY:

710242

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31578

American (AMR)

AF:

0.0000275

AC:

AN:

36366

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

111

AN:

24010

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.000299

AC:

AN:

80134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52868

Middle Eastern (MID)

AF:

0.000539

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.0000382

AC:

AN:

1099542

Other (OTH)

AF:

0.000390

AC:

AN:

58910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

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:

0.000280

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000222

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.10

(source)

DANN

Benign

0.34

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.33

M_CAP

Benign

0.00046

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.94

PhyloP100

-0.70

PROVEAN

Benign

1.0

REVEL

Benign

0.013

Sift

Benign

0.54

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.060

MVP

0.11

ClinPred

0.019

GERP RS

-0.32

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over