rs57914590

Positions:

• chr15-55491144-G-A
• chr15-55491144-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_130810.4(DNAAF4):​c.384C>T​(p.Tyr128Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000764 in 1,613,992 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00044 (4 hom.)
• Consequence: DNAAF4 NM_130810.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.108

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 15-55491144-G-A is Benign according to our data. Variant chr15-55491144-G-A is described in ClinVar as [Benign]. Clinvar id is 241832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.108 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00384 (585/152240) while in subpopulation AFR AF= 0.0135 (560/41530). AF 95% confidence interval is 0.0126. There are 4 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.384C>T	p.Tyr128Tyr	synonymous_variant	4/10	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.384C>T	p.Tyr128Tyr	synonymous_variant	4/9		NP_001028732.1
DNAAF4	NM_001033559.3	c.384C>T	p.Tyr128Tyr	synonymous_variant	4/9		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.639C>T		non_coding_transcript_exon_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.384C>T	p.Tyr128Tyr	synonymous_variant	4/10	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 585 AN: 152122 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00101 AC: 255 AN: 251372 Hom.: 3 AF XY: 0.000685 AC XY: 93 AN XY: 135862

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000443 AC: 648 AN: 1461752 Hom.: 4 Cov.: 30 AF XY: 0.000386 AC XY: 281 AN XY: 727172

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000701

Gnomad4 OTH exome AF: 0.000596

GnomAD4 genome AF: 0.00384 AC: 585 AN: 152240 Hom.: 4 Cov.: 31 AF XY: 0.00373 AC XY: 278 AN XY: 74446

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00436

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	5.0
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

Other links and lift over

dbSNP: rs57914590; hg19: chr15-55783342;