5-119165286-TAAAAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr5-119165286-T-TA
• rs11301800
• NM_001290321.3:c.4970+24dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000539542.6(DMXL1):​c.4970+6_4970+7insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (247 hom., cov: 0)
  • Exomes 𝑓: 0.027 (2 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

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+24dupA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+24dupA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+24dupA		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+7insA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+6_4970+7insA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+6_4325+7insA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 7454 AN: 114186 Hom.: 248 Cov.: 0

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0512

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0720

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0673

GnomAD2 exomes AF: 0.0138 AC: 1199 AN: 86686 AF XY: 0.0134

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0187

Gnomad EAS exome AF: 0.00516

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0266 AC: 20420 AN: 768080 Hom.: 2 Cov.: 0 AF XY: 0.0260 AC XY: 10329 AN XY: 397730

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

African (AFR) AF: 0.0171 AC: 305 AN: 17796

American (AMR) AF: 0.0147 AC: 327 AN: 22188

Ashkenazi Jewish (ASJ) AF: 0.0270 AC: 447 AN: 16546

East Asian (EAS) AF: 0.00410 AC: 132 AN: 32206

South Asian (SAS) AF: 0.0296 AC: 1411 AN: 47684

European-Finnish (FIN) AF: 0.0262 AC: 992 AN: 37884

Middle Eastern (MID) AF: 0.0224 AC: 59 AN: 2636

European-Non Finnish (NFE) AF: 0.0286 AC: 15896 AN: 556470

Other (OTH) AF: 0.0245 AC: 851 AN: 34670

⚠️ 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: 0.0652 AC: 7449 AN: 114178 Hom.: 247 Cov.: 0 AF XY: 0.0676 AC XY: 3691 AN XY: 54624

African (AFR) AF: 0.0390 AC: 1190 AN: 30480

American (AMR) AF: 0.0643 AC: 735 AN: 11436

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 265 AN: 2810

East Asian (EAS) AF: 0.00332 AC: 15 AN: 4522

South Asian (SAS) AF: 0.101 AC: 362 AN: 3598

European-Finnish (FIN) AF: 0.111 AC: 621 AN: 5570

Middle Eastern (MID) AF: 0.0748 AC: 16 AN: 214

European-Non Finnish (NFE) AF: 0.0770 AC: 4104 AN: 53286

Other (OTH) AF: 0.0670 AC: 107 AN: 1598

Alfa AF: 0.0153 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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11301800; hg19: chr5-118500981;