15-55430791-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_130810.4(DNAAF4):c.1154-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,580,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

DNAAF4
NM_130810.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002911

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.826

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-55430791-T-C is Benign according to our data. Variant chr15-55430791-T-C is described in ClinVar as [Benign]. Clinvar id is 1528086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00137 (208/152334) while in subpopulation AMR AF= 0.0051 (78/15288). AF 95% confidence interval is 0.00419. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DNAAF4	NM_130810.4 linkuse as main transcript	c.1154-12A>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1 linkuse as main transcript	n.1408+1706A>G	intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3 linkuse as main transcript	c.1048-12A>G	splice_polypyrimidine_tract_variant, intron_variant
DNAAF4	NM_001033560.2 linkuse as main transcript	c.1047+4114A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7 linkuse as main transcript	c.1154-12A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_130810.4	P1	Q8WXU2-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00121

AC:

297

AN:

246444

Hom.:

AF XY:

0.00113

AC XY:

151

AN XY:

133064

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00303

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.00233

GnomAD4 exome

AF:

0.00130

AC:

1860

AN:

1427698

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

902

AN XY:

712070

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00124

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.000207

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152334

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000556

Hom.:

Bravo

AF:

0.00177

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.13

Dann

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.090

SpliceAI score (max)

0.050

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