15-55468324-T-C

Variant names:

• chr15-55468324-T-C
• rs692690
• NM_130810.4:c.406-1163A>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.406-1163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,022 control chromosomes in the GnomAD database, including 23,091 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 0.53 (23091 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_130810.4	MANE Select	c.406-1163A>G		intron	N/A	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033560.2		c.406-1163A>G		intron	N/A	NP_001028732.1	Q8WXU2-2
	DNAAF4	NM_001033559.3		c.406-1163A>G		intron	N/A	NP_001028731.1	Q8WXU2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.406-1163A>G		intron	N/A	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000448430.6	TSL:1	c.406-1163A>G		intron	N/A	ENSP00000403412.2	Q8WXU2-2
	DNAAF4	ENST00000457155.6	TSL:1	c.406-1163A>G		intron	N/A	ENSP00000402640.2	Q8WXU2-3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80352 AN: 151904 Hom.: 23081 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.529 AC: 80389 AN: 152022 Hom.: 23091 Cov.: 32 AF XY: 0.536 AC XY: 39823 AN XY: 74304

African (AFR) AF: 0.312 AC: 12947 AN: 41470

American (AMR) AF: 0.672 AC: 10255 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4617 AN: 5174

South Asian (SAS) AF: 0.684 AC: 3297 AN: 4822

European-Finnish (FIN) AF: 0.596 AC: 6291 AN: 10548

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38988 AN: 67964

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.565 Hom.: 12560

Bravo AF: 0.528

Asia WGS AF: 0.751 AC: 2609 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		-0.20
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: rs692690; hg19: chr15-55760522;