rs12594443

Positions:

• chr15-55497280-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130810.4(DNAAF4):​c.271+432T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,154 control chromosomes in the GnomAD database, including 268 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 0.050 (268 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.271+432T>C		intron_variant		ENST00000321149.7	NP_570722.2
DNAAF4-CCPG1	NR_037923.1	n.526+432T>C		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.271+432T>C		intron_variant			NP_001028731.1
DNAAF4	NM_001033560.2	c.271+432T>C		intron_variant			NP_001028732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+432T>C		intron_variant		1	NM_130810.4	ENSP00000323275	P1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7659 AN: 152036 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0638

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0493

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

GnomAD4 genome AF: 0.0504 AC: 7664 AN: 152154 Hom.: 268 Cov.: 32 AF XY: 0.0506 AC XY: 3760 AN XY: 74380

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0638

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0487 Hom.: 31

Bravo AF: 0.0484

Asia WGS AF: 0.122 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs12594443; hg19: chr15-55789478;