5-119165286-TAAAAAAAAAAA-TAAAAAAAAAAAA

Position:

• chr5-119165286-TAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001290321.3(DMXL1):​c.4970+24dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (247 hom., cov: 0)
  • Exomes 𝑓: 0.027 (2 hom.)
• Consequence: DMXL1 NM_001290321.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1	NM_001290321.3	c.4970+24dup		splice_region_variant, intron_variant		ENST00000539542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMXL1	ENST00000539542.6	c.4970+24dup		splice_region_variant, intron_variant		1	NM_001290321.3	A1
DMXL1	ENST00000311085.8	c.4970+24dup		splice_region_variant, intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 7454 AN: 114186 Hom.: 248 Cov.: 0

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0512

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0720

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0673

GnomAD3 exomes AF: 0.0138 AC: 1199 AN: 86686 Hom.: 0 AF XY: 0.0134 AC XY: 638 AN XY: 47508

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0187

Gnomad EAS exome AF: 0.00516

Gnomad SAS exome AF: 0.0148

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0266 AC: 20420 AN: 768080 Hom.: 2 Cov.: 0 AF XY: 0.0260 AC XY: 10329 AN XY: 397730

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.00410

Gnomad4 SAS exome AF: 0.0296

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0652 AC: 7449 AN: 114178 Hom.: 247 Cov.: 0 AF XY: 0.0676 AC XY: 3691 AN XY: 54624

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.00332

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs11301800; hg19: chr5-118500981;