NM_130810.4:c.1204G>C

Variant names:

• chr15-55430729-C-G
• rs200856356
• NM_130810.4:c.1204G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_130810.4(DNAAF4):​c.1204G>C​(p.Val402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V402A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: DNAAF4 NM_130810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08670008).

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.1204G>C	p.Val402Leu	missense	Exon 10 of 10	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033559.3		c.1098G>C	p.Leu366Phe	missense	Exon 9 of 9	NP_001028731.1	Q8WXU2-3
	DNAAF4	NM_001033560.2		c.1047+4176G>C		intron	N/A	NP_001028732.1	Q8WXU2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.1204G>C	p.Val402Leu	missense	Exon 10 of 10	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000457155.6	TSL:1	c.1098G>C	p.Leu366Phe	missense	Exon 8 of 8	ENSP00000402640.2	Q8WXU2-3
	DNAAF4	ENST00000448430.6	TSL:1	c.1047+4176G>C		intron	N/A	ENSP00000403412.2	Q8WXU2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251300 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461058 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726866

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111566

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.3
DANN	Benign	0.61
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.050
PROVEAN	Benign	0.77	N
REVEL	Benign	0.020
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.13	B
Vest4		0.18
MutPred		0.40		Loss of loop (P = 9e-04)
MVP		0.23
ClinPred		0.058	T
GERP RS		3.7
Varity_R		0.039
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs200856356; hg19: chr15-55722927;