rs3743205

Variant names:

• chr15-55498332-C-T
• rs3743205
• NM_130810.4:c.-3G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-55498332-C-T
• chr15-55498332-C-A
• chr15-55498332-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130810.4(DNAAF4):​c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,598,830 control chromosomes in the GnomAD database, including 4,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1143 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3757 hom.)
• Consequence: DNAAF4 NM_130810.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: 0.601
• Publications: 49 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 15-55498332-C-T is Benign according to our data. Variant chr15-55498332-C-T is described in ClinVar as Benign. ClinVar VariationId is 2135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_130810.4	MANE Select	c.-3G>A		5_prime_UTR	Exon 2 of 10	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033560.2		c.-3G>A		5_prime_UTR	Exon 2 of 9	NP_001028732.1	Q8WXU2-2
	DNAAF4	NM_001033559.3		c.-3G>A		5_prime_UTR	Exon 2 of 9	NP_001028731.1	Q8WXU2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.-3G>A		5_prime_UTR	Exon 2 of 10	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000448430.6	TSL:1	c.-3G>A		5_prime_UTR	Exon 1 of 8	ENSP00000403412.2	Q8WXU2-2
	DNAAF4	ENST00000457155.6	TSL:1	c.-3G>A		5_prime_UTR	Exon 1 of 8	ENSP00000402640.2	Q8WXU2-3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15603 AN: 152064 Hom.: 1136 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0935

GnomAD2 exomes AF: 0.0718 AC: 17165 AN: 239114 AF XY: 0.0724

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0429

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0350

Gnomad FIN exome AF: 0.0535

Gnomad NFE exome AF: 0.0615

Gnomad OTH exome AF: 0.0759

GnomAD4 exome AF: 0.0664 AC: 96128 AN: 1446648 Hom.: 3757 Cov.: 32 AF XY: 0.0674 AC XY: 48373 AN XY: 717954

African (AFR) AF: 0.201 AC: 6563 AN: 32620

American (AMR) AF: 0.0462 AC: 1983 AN: 42964

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2858 AN: 25876

East Asian (EAS) AF: 0.0359 AC: 1386 AN: 38588

South Asian (SAS) AF: 0.0976 AC: 8266 AN: 84690

European-Finnish (FIN) AF: 0.0570 AC: 3039 AN: 53300

Middle Eastern (MID) AF: 0.112 AC: 636 AN: 5690

European-Non Finnish (NFE) AF: 0.0606 AC: 66808 AN: 1103212

Other (OTH) AF: 0.0769 AC: 4589 AN: 59708

GnomAD4 genome AF: 0.103 AC: 15637 AN: 152182 Hom.: 1143 Cov.: 32 AF XY: 0.102 AC XY: 7618 AN XY: 74422

African (AFR) AF: 0.205 AC: 8500 AN: 41498

American (AMR) AF: 0.0755 AC: 1155 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3466

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5176

South Asian (SAS) AF: 0.0903 AC: 436 AN: 4828

European-Finnish (FIN) AF: 0.0580 AC: 615 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4162 AN: 68016

Other (OTH) AF: 0.0920 AC: 194 AN: 2108

Alfa AF: 0.0753 Hom.: 947

Bravo AF: 0.106

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	-	Dyslexia, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.60
PromoterAI		-0.060	Neutral
Mutation Taster		=300/0	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: rs3743205; hg19: chr15-55790530; COSMIC: COSV58247781;