5-119165286-TAAAAAAAAAAA-TAAAAAA

Position:

• chr5-119165286-TAAAAAAAAAAA-TAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000539542.6(DMXL1):​c.4970+20_4970+24del variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00446 in 878,316 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (0 hom.)
• Consequence: DMXL1 ENST00000539542.6 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.4970+20_4970+24del		splice_region_variant, intron_variant		ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMXL1	ENST00000539542.6	c.4970+20_4970+24del		splice_region_variant, intron_variant		1	NM_001290321.3	ENSP00000439479	A1
DMXL1	ENST00000311085.8	c.4970+20_4970+24del		splice_region_variant, intron_variant		1		ENSP00000309690	P3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 3 AN: 114276 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000375

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00729 AC: 632 AN: 86686 Hom.: 0 AF XY: 0.00730 AC XY: 347 AN XY: 47508

Gnomad AFR exome AF: 0.00446

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00572

Gnomad EAS exome AF: 0.0118

Gnomad SAS exome AF: 0.0135

Gnomad FIN exome AF: 0.00353

Gnomad NFE exome AF: 0.00522

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00512 AC: 3914 AN: 764040 Hom.: 0 AF XY: 0.00518 AC XY: 2050 AN XY: 395454

Gnomad4 AFR exome AF: 0.00498

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00504

Gnomad4 EAS exome AF: 0.00777

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.00470

Gnomad4 NFE exome AF: 0.00436

Gnomad4 OTH exome AF: 0.00540

GnomAD4 genome AF: 0.0000263 AC: 3 AN: 114276 Hom.: 0 Cov.: 0 AF XY: 0.0000366 AC XY: 2 AN XY: 54654

Gnomad4 AFR AF: 0.0000328

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000375

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;