15-55418091-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001033560.2(DNAAF4):​c.1090C>A​(p.Pro364Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DNAAF4
NM_001033560.2 missense

Scores

15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.698
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]
PIERCE2 (HGNC:44654): (piercer of microtubule wall 2)
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057718337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIERCE2NM_001198784.2 linkc.19-132G>T intron_variant Intron 1 of 1 ENST00000569691.2 NP_001185713.1 H3BRN8
DNAAF4NM_001033560.2 linkc.1090C>A p.Pro364Thr missense_variant Exon 9 of 9 NP_001028732.1 Q8WXU2-2A0A0S2Z5Z4
DNAAF4-CCPG1NR_037923.1 linkn.1408+14406C>A intron_variant Intron 8 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIERCE2ENST00000569691.2 linkc.19-132G>T intron_variant Intron 1 of 1 1 NM_001198784.2 ENSP00000456337.1 H3BRN8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1428522
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
710242
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.2
DANN
Benign
0.32
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.00057
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.00052
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-0.97
T
PROVEAN
Benign
0.15
N
REVEL
Benign
0.022
Sift
Benign
0.23
T
Sift4G
Benign
0.60
T
Polyphen
0.0010
B
Vest4
0.099
MutPred
0.27
Gain of helix (P = 0.0128);
MVP
0.13
ClinPred
0.093
T
GERP RS
-0.32

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.

Other links and lift over

dbSNP: rs199564997; hg19: chr15-55710289; API