Genetic Variant DNAAF4:p.His362Arg (chr15-55430742-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_130810.4(DNAAF4):c.1191A>G(p.Pro397Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DNAAF4
NM_130810.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.613

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.063753456).

BP6

Variant 15-55430742-T-C is Benign according to our data. Variant chr15-55430742-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1540572.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.613 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4 link	c.1191A>G	p.Pro397Pro	synonymous_variant	Exon 10 of 10	ENST00000321149.7	NP_570722.2	Q8WXU2-1
DNAAF4	NM_001033559.3 link	c.1085A>G	p.His362Arg	missense_variant	Exon 9 of 9		NP_001028731.1	Q8WXU2-3
DNAAF4	NM_001033560.2 link	c.1047+4163A>G		intron_variant	Intron 8 of 8		NP_001028732.1	Q8WXU2-2A0A0S2Z5Z4
DNAAF4-CCPG1	NR_037923.1 link	n.1408+1755A>G		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 link	c.1191A>G	p.Pro397Pro	synonymous_variant	Exon 10 of 10	1	NM_130810.4	ENSP00000323275.3		Q8WXU2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461174

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.000101

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111614

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.2

(source)

DANN

Benign

0.97

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.41

M_CAP

Benign

0.0025

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.96

PhyloP100

0.61

PROVEAN

Benign

2.4

REVEL

Benign

0.048

Sift

Benign

0.10

Sift4G

Benign

0.092

Polyphen

0.0040

Vest4

0.12

MutPred

0.52

Loss of loop (P = 0.0022);

MVP

0.35

ClinPred

0.10

GERP RS

3.3

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over