chr15-55498332-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 0.601

Variant links:

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 links:

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]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4 link	c.-3G>A	5_prime_UTR_variant	Exon 2 of 10	ENST00000321149.7	NP_570722.2	Q8WXU2-1
DNAAF4	NM_001033560.2 link	c.-3G>A	5_prime_UTR_variant	Exon 2 of 9		NP_001028732.1	Q8WXU2-2A0A0S2Z5Z4
DNAAF4	NM_001033559.3 link	c.-3G>A	5_prime_UTR_variant	Exon 2 of 9		NP_001028731.1	Q8WXU2-3
DNAAF4-CCPG1	NR_037923.1 link	n.253G>A	non_coding_transcript_exon_variant	Exon 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 link	c.-3G>A		5_prime_UTR_variant	Exon 2 of 10	1	NM_130810.4	ENSP00000323275.3		Q8WXU2-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15603

AN:

152064

Hom.:

1136

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0718

AC:

17165

AN:

239114

Hom.:

878

AF XY:

0.0724

AC XY:

9396

AN XY:

129714

show subpopulations

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 SAS exome

AF:

0.0951

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.:

AF XY:

0.0674

AC XY:

48373

AN XY:

717954

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0462

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0359

Gnomad4 SAS exome

AF:

0.0976

Gnomad4 FIN exome

AF:

0.0570

Gnomad4 NFE exome

AF:

0.0606

Gnomad4 OTH exome

AF:

0.0769

GnomAD4 genome

AF:

0.103

AC:

15637

AN:

152182

Hom.:

1143

Cov.:

AF XY:

0.102

AC XY:

7618

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.0340

Gnomad4 SAS

AF:

0.0903

Gnomad4 FIN

AF:

0.0580

Gnomad4 NFE

AF:

0.0612

Gnomad4 OTH

AF:

0.0920

Alfa

AF:

0.0711

Hom.:

668

Bravo

AF:

0.106

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 12954984, 22383464, 18445785, 23065966, 23341075) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, variant associated with dyslexia -

Dyslexia, susceptibility to, 1

Other:1

Sep 30, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over