5-119165286-TAAAAAAAAAAA-TAAAAAAAAA

Position:

• chr5-119165286-TAAAAAAAAAAA-TAAAAAAAAA

Variant summary

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

The NM_001290321.3(DMXL1):​c.4970+23_4970+24del variant causes a splice region, intron change. The variant allele was found at a frequency of 0.136 in 852,954 control chromosomes in the GnomAD database, including 43 homozygotes. 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 0.014 (25 hom., cov: 0)
  • Exomes 𝑓: 0.16 (18 hom.)
• Consequence: DMXL1 NM_001290321.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 (EAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1	NM_001290321.3	c.4970+23_4970+24del		splice_region_variant, intron_variant		ENST00000539542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMXL1	ENST00000539542.6	c.4970+23_4970+24del		splice_region_variant, intron_variant		1	NM_001290321.3	A1
DMXL1	ENST00000311085.8	c.4970+23_4970+24del		splice_region_variant, intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 1576 AN: 114210 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00676

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.00503

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.0194

GnomAD3 exomes AF: 0.191 AC: 16531 AN: 86686 Hom.: 5 AF XY: 0.194 AC XY: 9239 AN XY: 47508

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.155 AC: 114591 AN: 738752 Hom.: 18 AF XY: 0.157 AC XY: 59958 AN XY: 381412

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.0138 AC: 1579 AN: 114202 Hom.: 25 Cov.: 0 AF XY: 0.0150 AC XY: 821 AN XY: 54630

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.00676

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.0445

Gnomad4 FIN AF: 0.00503

Gnomad4 NFE AF: 0.00910

Gnomad4 OTH AF: 0.0237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11301800; hg19: chr5-118500981;