5-119165286-TAAAAAAAAAAA-TAAAAA

Variant names:

• chr5-119165286-TAAAAAA-T
• rs11301800
• NM_001290321.3:c.4970+19_4970+24delAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539542.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	NM_001290321.3	MANE Select	c.4970+19_4970+24delAAAAAA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+19_4970+24delAAAAAA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+19_4970+24delAAAAAA		intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.4970+7_4970+12delAAAAAA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+7_4970+12delAAAAAA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+7_4325+12delAAAAAA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

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

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000505 AC: 9 AN: 17810

American (AMR) AF: 0.00171 AC: 38 AN: 22210

Ashkenazi Jewish (ASJ) AF: 0.000904 AC: 15 AN: 16598

East Asian (EAS) AF: 0.00112 AC: 36 AN: 32204

South Asian (SAS) AF: 0.00191 AC: 91 AN: 47758

European-Finnish (FIN) AF: 0.000843 AC: 32 AN: 37972

Middle Eastern (MID) AF: 0.000756 AC: 2 AN: 2644

European-Non Finnish (NFE) AF: 0.000610 AC: 340 AN: 557170

Other (OTH) AF: 0.000748 AC: 26 AN: 34744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 30460

American (AMR) AF: 0.00 AC: 0 AN: 11428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2814

East Asian (EAS) AF: 0.00 AC: 0 AN: 4542

South Asian (SAS) AF: 0.00 AC: 0 AN: 3622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53340

Other (OTH) AF: 0.00 AC: 0 AN: 1598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11301800; hg19: chr5-118500981;