15-55466995-T-C

Position:

chr15-55466995-T-C

Variant summary

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

The NM_130810.4(DNAAF4):c.572A>G(p.Glu191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,580,218 control chromosomes in the GnomAD database, including 215,443 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18831 hom., cov: 32)

Exomes 𝑓: 0.52 ( 196612 hom. )

Consequence

DNAAF4
NM_130810.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.27

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:):

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 (MetaRNN=1.2143059E-6).

BP6

Variant 15-55466995-T-C is Benign according to our data. Variant chr15-55466995-T-C is described in ClinVar as [Benign]. Clinvar id is 262315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAAF4	NM_130810.4 linkuse as main transcript	c.572A>G	p.Glu191Gly	missense_variant	5/10	ENST00000321149.7	NP_570722.2
DNAAF4-CCPG1	NR_037923.1 linkuse as main transcript	n.827A>G		non_coding_transcript_exon_variant	4/16
DNAAF4	NM_001033560.2 linkuse as main transcript	c.572A>G	p.Glu191Gly	missense_variant	5/9		NP_001028732.1
DNAAF4	NM_001033559.3 linkuse as main transcript	c.572A>G	p.Glu191Gly	missense_variant	5/9		NP_001028731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 linkuse as main transcript	c.572A>G	p.Glu191Gly	missense_variant	5/10	1	NM_130810.4	ENSP00000323275	P1	Q8WXU2-1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73377

AN:

151740

Hom.:

18816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.518

GnomAD3 exomes

AF:

0.565

AC:

122158

AN:

216136

Hom.:

35582

AF XY:

0.558

AC XY:

65918

AN XY:

118074

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.738

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.766

Gnomad SAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.520

AC:

743283

AN:

1428360

Hom.:

196612

Cov.:

AF XY:

0.520

AC XY:

369290

AN XY:

709884

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.744

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.557

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.483

AC:

73419

AN:

151858

Hom.:

18831

Cov.:

AF XY:

0.490

AC XY:

36380

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.625

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.744

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.518

Hom.:

46857

Bravo

AF:

0.487

TwinsUK

AF:

0.493

AC:

1829

ALSPAC

AF:

0.516

AC:

1990

ESP6500AA

AF:

0.314

AC:

1360

ESP6500EA

AF:

0.521

AC:

4448

ExAC

AF:

0.543

AC:

65369

Asia WGS

AF:

0.628

AC:

2172

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 28, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 25

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

.;.;T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.46

T;T;T;.

MetaRNN

Benign

0.0000012

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.81

P;P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;N;N;D

REVEL

Benign

0.061

Sift

Benign

0.081

T;D;D;D

Sift4G

Uncertain

0.035

D;D;D;D

Polyphen

0.021

B;B;B;B

Vest4

0.18

MPC

0.054

ClinPred

0.010

GERP RS

2.5

Varity_R

0.10

gMVP

0.32

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