15-55438983-C-T

Variant names:

• chr15-55438983-C-T
• rs687623
• NM_130810.4:c.893+489G>A

Variant summary

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

The NM_130810.4(DNAAF4):​c.893+489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,962 control chromosomes in the GnomAD database, including 24,190 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 0.55 (24190 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_130810.4	MANE Select	c.893+489G>A		intron	N/A	NP_570722.2
	DNAAF4	NM_001033560.2		c.893+489G>A		intron	N/A	NP_001028732.1
	DNAAF4	NM_001033559.3		c.893+489G>A		intron	N/A	NP_001028731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.893+489G>A		intron	N/A	ENSP00000323275.3
	DNAAF4	ENST00000448430.6	TSL:1	c.893+489G>A		intron	N/A	ENSP00000403412.2
	DNAAF4	ENST00000457155.6	TSL:1	c.893+489G>A		intron	N/A	ENSP00000402640.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83040 AN: 151840 Hom.: 24167 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.547 AC: 83112 AN: 151962 Hom.: 24190 Cov.: 32 AF XY: 0.553 AC XY: 41069 AN XY: 74250

African (AFR) AF: 0.362 AC: 15012 AN: 41416

American (AMR) AF: 0.681 AC: 10394 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2253 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4770 AN: 5184

South Asian (SAS) AF: 0.681 AC: 3283 AN: 4822

European-Finnish (FIN) AF: 0.605 AC: 6381 AN: 10544

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39098 AN: 67954

Other (OTH) AF: 0.584 AC: 1230 AN: 2106

Alfa AF: 0.574 Hom.: 101865

Bravo AF: 0.547

Asia WGS AF: 0.780 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.51
DANN	Benign	0.64
PhyloP100		-0.98
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: rs687623; hg19: chr15-55731181;