NM_130810.4:c.406-10612A>G

Variant names:

• chr15-55477773-T-C
• rs4144134
• NM_130810.4:c.406-10612A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130810.4(DNAAF4):​c.406-10612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,566 control chromosomes in the GnomAD database, including 20,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (20629 hom., cov: 29)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 4 publications found

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-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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.406-10612A>G		intron_variant	Intron 4 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.406-10612A>G		intron_variant	Intron 4 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.406-10612A>G		intron_variant	Intron 4 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.661-10612A>G		intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.406-10612A>G		intron_variant	Intron 4 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76069 AN: 151452 Hom.: 20618 Cov.: 29

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.502 AC: 76101 AN: 151566 Hom.: 20629 Cov.: 29 AF XY: 0.507 AC XY: 37537 AN XY: 74028

African (AFR) AF: 0.290 AC: 11973 AN: 41338

American (AMR) AF: 0.651 AC: 9867 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2075 AN: 3466

East Asian (EAS) AF: 0.748 AC: 3854 AN: 5152

South Asian (SAS) AF: 0.563 AC: 2696 AN: 4792

European-Finnish (FIN) AF: 0.580 AC: 6066 AN: 10456

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37794 AN: 67894

Other (OTH) AF: 0.539 AC: 1132 AN: 2100

Alfa AF: 0.511 Hom.: 2505

Bravo AF: 0.503

Asia WGS AF: 0.637 AC: 2216 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4144134; hg19: chr15-55769971;