rs600753

Positions:

• chr15-55466995-T-A
• chr15-55466995-T-C
• chr15-55466995-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_130810.4(DNAAF4):​c.572A>T​(p.Glu191Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DNAAF4 NM_130810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.572A>T	p.Glu191Val	missense_variant	5/10	ENST00000321149.7	NP_570722.2
DNAAF4-CCPG1	NR_037923.1	n.827A>T		non_coding_transcript_exon_variant	4/16
DNAAF4	NM_001033560.2	c.572A>T	p.Glu191Val	missense_variant	5/9		NP_001028732.1
DNAAF4	NM_001033559.3	c.572A>T	p.Glu191Val	missense_variant	5/9		NP_001028731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.572A>T	p.Glu191Val	missense_variant	5/10	1	NM_130810.4	ENSP00000323275	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0075	.;.;T;T
Eigen	Benign	-0.032
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.60	T;T;T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.67	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.016	D;D;D;D
Sift4G	Benign	0.072	T;T;T;T
Polyphen		0.96	D;P;P;P
Vest4		0.30
MutPred		0.19		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.70
MPC		0.10
ClinPred		0.78	D
GERP RS		2.5
Varity_R		0.14
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.96		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.96		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs600753; hg19: chr15-55759193;