Genetic Variant DMXL1:c.4970+20_4970+24dupAAAAA (chr5-119165286-T-TAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000539542.6(DMXL1):c.4970+6_4970+7insAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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: 0.0000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DMXL1
ENST00000539542.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.401

Publications

0 publications found

Variant links:

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]

DMXL1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMXL1	NM_001290321.3	MANE Select	c.4970+20_4970+24dupAAAAA	intron	N/A	NP_001277250.1	F5H269
DMXL1	NM_001349239.2		c.4970+20_4970+24dupAAAAA	intron	N/A	NP_001336168.1	F5H269
DMXL1	NM_001349240.2		c.4970+20_4970+24dupAAAAA	intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

114286

Hom.:

Cov.:

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:

0.00000130

AC:

AN:

770324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

398888

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

17838

American (AMR)

AF:

0.00

AC:

AN:

22268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16620

East Asian (EAS)

AF:

0.00

AC:

AN:

32276

South Asian (SAS)

AF:

0.00

AC:

AN:

47912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2646

European-Non Finnish (NFE)

AF:

0.00000179

AC:

AN:

557912

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

114286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54660

African (AFR)

AF:

0.00

AC:

AN:

30460

American (AMR)

AF:

0.00

AC:

AN:

11428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2814

East Asian (EAS)

AF:

0.00

AC:

AN:

4542

South Asian (SAS)

AF:

0.00

AC:

AN:

3622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53342

Other (OTH)

AF:

0.00

AC:

AN:

1598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over