5-119165286-TAAAAAAAAAAA-TAAAAA

Variant names:

• chr5-119165286-TAAAAAA-T
• NM_001290321.3:c.4970+19_4970+24delAAAAAA

Variant summary

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

The ENST00000539542.6(DMXL1):​c.4970+7_4970+12delAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000766 in 769,110 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00077 (0 hom.)
  • Failed GnomAD Quality Control
• 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 rank	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.4970+19_4970+24delAAAAAA		intron_variant	Intron 21 of 43	ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMXL1	ENST00000539542.6	c.4970+7_4970+12delAAAAAA		splice_region_variant, intron_variant	Intron 21 of 43	1	NM_001290321.3	ENSP00000439479.1
DMXL1	ENST00000311085.8	c.4970+7_4970+12delAAAAAA		splice_region_variant, intron_variant	Intron 21 of 42	1		ENSP00000309690.8

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 114284 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000766 AC: 589 AN: 769110 Hom.: 0 AF XY: 0.000773 AC XY: 308 AN XY: 398194

Gnomad4 AFR exome AF: 0.000505

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.000904

Gnomad4 EAS exome AF: 0.00112

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.000843

Gnomad4 NFE exome AF: 0.000610

Gnomad4 OTH exome AF: 0.000748

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 114284 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54658

Gnomad4 AFR AF: 0.00

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: 0.00

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-118500981;