5-119165286-TAAAAAAAAAAA-TAAAAAAAA

Position:

• chr5-119165286-TAAAAAAAAAAA-TAAAAAAAA

Variant summary

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

The NM_001290321.3(DMXL1):​c.4970+22_4970+24del variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0551 in 855,778 control chromosomes in the GnomAD database, including 10 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 0.0051 (8 hom., cov: 0)
  • Exomes 𝑓: 0.063 (2 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: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1	NM_001290321.3	c.4970+22_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+22_4970+24del		splice_region_variant, intron_variant		1	NM_001290321.3	A1
DMXL1	ENST00000311085.8	c.4970+22_4970+24del		splice_region_variant, intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 584 AN: 114254 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.000711

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00689

GnomAD3 exomes AF: 0.0852 AC: 7389 AN: 86686 Hom.: 2 AF XY: 0.0874 AC XY: 4150 AN XY: 47508

Gnomad AFR exome AF: 0.0723

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0899

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.0691

Gnomad OTH exome AF: 0.0874

GnomAD4 exome AF: 0.0628 AC: 46593 AN: 741534 Hom.: 2 AF XY: 0.0644 AC XY: 24653 AN XY: 382966

Gnomad4 AFR exome AF: 0.0658

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0958

Gnomad4 FIN exome AF: 0.0543

Gnomad4 NFE exome AF: 0.0557

Gnomad4 OTH exome AF: 0.0672

GnomAD4 genome AF: 0.00512 AC: 585 AN: 114244 Hom.: 8 Cov.: 0 AF XY: 0.00664 AC XY: 363 AN XY: 54656

Gnomad4 AFR AF: 0.00121

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.000711

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00748

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;