5-119165286-TAAAAAAAAAAA-TAAAAAAAAAAAAA

Variant names:

• chr5-119165286-T-TAA
• rs11301800
• NM_001290321.3:c.4970+23_4970+24dupAA

Variant summary

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

The ENST00000539542.6(DMXL1):​c.4970+6_4970+7insAA 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 0.00064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: DMXL1 ENST00000539542.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• 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+23_4970+24dupAA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+23_4970+24dupAA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+23_4970+24dupAA		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+6_4970+7insAA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+6_4970+7insAA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+6_4325+7insAA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes AF: 0.000639 AC: 73 AN: 114280 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000875

Gnomad ASJ AF: 0.000711

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.000487

Gnomad OTH AF: 0.00125

GnomAD4 exome AF: 0.00158 AC: 1219 AN: 769622 Hom.: 0 Cov.: 0 AF XY: 0.00160 AC XY: 636 AN XY: 398502

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

African (AFR) AF: 0.00157 AC: 28 AN: 17820

American (AMR) AF: 0.00103 AC: 23 AN: 22244

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 26 AN: 16612

East Asian (EAS) AF: 0.000186 AC: 6 AN: 32268

South Asian (SAS) AF: 0.00307 AC: 147 AN: 47850

European-Finnish (FIN) AF: 0.00129 AC: 49 AN: 38024

Middle Eastern (MID) AF: 0.00189 AC: 5 AN: 2646

European-Non Finnish (NFE) AF: 0.00160 AC: 892 AN: 557386

Other (OTH) AF: 0.00124 AC: 43 AN: 34772

⚠️ 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 AF: 0.000639 AC: 73 AN: 114272 Hom.: 0 Cov.: 0 AF XY: 0.000567 AC XY: 31 AN XY: 54674

African (AFR) AF: 0.00121 AC: 37 AN: 30500

American (AMR) AF: 0.0000874 AC: 1 AN: 11440

Ashkenazi Jewish (ASJ) AF: 0.000711 AC: 2 AN: 2814

East Asian (EAS) AF: 0.00 AC: 0 AN: 4524

South Asian (SAS) AF: 0.000833 AC: 3 AN: 3600

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

Middle Eastern (MID) AF: 0.00935 AC: 2 AN: 214

European-Non Finnish (NFE) AF: 0.000488 AC: 26 AN: 53330

Other (OTH) AF: 0.00125 AC: 2 AN: 1606

Alfa AF: 0.00 Hom.: 74

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
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;