15-55495055-T-C

Variant names:

• chr15-55495055-T-C
• rs16976343
• NM_130810.4:c.271+2657A>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.271+2657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,636 control chromosomes in the GnomAD database, including 9,738 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 0.28 (9738 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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.271+2657A>G		intron	N/A	NP_570722.2
	DNAAF4	NM_001033560.2		c.271+2657A>G		intron	N/A	NP_001028732.1
	DNAAF4	NM_001033559.3		c.271+2657A>G		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.271+2657A>G		intron	N/A	ENSP00000323275.3
	DNAAF4	ENST00000448430.6	TSL:1	c.271+2657A>G		intron	N/A	ENSP00000403412.2
	DNAAF4	ENST00000457155.6	TSL:1	c.271+2657A>G		intron	N/A	ENSP00000402640.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42531 AN: 151510 Hom.: 9699 Cov.: 30

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.281 AC: 42625 AN: 151628 Hom.: 9738 Cov.: 30 AF XY: 0.277 AC XY: 20526 AN XY: 74118

African (AFR) AF: 0.637 AC: 26291 AN: 41272

American (AMR) AF: 0.164 AC: 2492 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3468

East Asian (EAS) AF: 0.186 AC: 955 AN: 5138

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1278 AN: 10482

Middle Eastern (MID) AF: 0.152 AC: 44 AN: 290

European-Non Finnish (NFE) AF: 0.135 AC: 9178 AN: 67906

Other (OTH) AF: 0.236 AC: 498 AN: 2106

Alfa AF: 0.169 Hom.: 10239

Bravo AF: 0.296

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		-0.0050
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: rs16976343; hg19: chr15-55787253;