5-119165286-TAAAAAAAAAAA-TAA

Variant names:

• chr5-119165286-TAAAAAAAAA-T
• rs11301800
• NM_001290321.3:c.4970+16_4970+24delAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000539542.6(DMXL1):​c.4970+7_4970+15delAAAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000013 in 770,322 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• 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 2 ACMG points.

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

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+16_4970+24delAAAAAAAAA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+16_4970+24delAAAAAAAAA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+16_4970+24delAAAAAAAAA		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+15delAAAAAAAAA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+7_4970+15delAAAAAAAAA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+7_4325+15delAAAAAAAAA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000130 AC: 1 AN: 770322 Hom.: 0 AF XY: 0.00000251 AC XY: 1 AN XY: 398888

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

African (AFR) AF: 0.00 AC: 0 AN: 17838

American (AMR) AF: 0.00 AC: 0 AN: 22268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16622

East Asian (EAS) AF: 0.00 AC: 0 AN: 32276

South Asian (SAS) AF: 0.00 AC: 0 AN: 47912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2646

European-Non Finnish (NFE) AF: 0.00000179 AC: 1 AN: 557910

Other (OTH) AF: 0.00 AC: 0 AN: 34790

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

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;