NM_130810.4:c.271+432T>C

Variant names:

• chr15-55497280-A-G
• rs12594443
• NM_130810.4:c.271+432T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.271+432T>C		intron_variant	Intron 3 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.271+432T>C		intron_variant	Intron 3 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.271+432T>C		intron_variant	Intron 3 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.526+432T>C		intron_variant	Intron 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+432T>C		intron_variant	Intron 3 of 9	1	NM_130810.4	ENSP00000323275.3

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

African (AFR) AF: 0.0175 AC: 725 AN: 41522

American (AMR) AF: 0.0481 AC: 735 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 221 AN: 3466

East Asian (EAS) AF: 0.149 AC: 770 AN: 5174

South Asian (SAS) AF: 0.138 AC: 663 AN: 4814

European-Finnish (FIN) AF: 0.0338 AC: 358 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4011 AN: 67994

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0587 Hom.: 108

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
PhyloP100		0.59
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: rs12594443; hg19: chr15-55789478;