5-119165286-TAAAAAAAAAAA-TAAAAAAAAA

Variant names:

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

Variant summary

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

The ENST00000539542.6(DMXL1):​c.4970+7_4970+8delAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.136 in 852,954 control chromosomes in the GnomAD database, including 43 homozygotes. 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 0.014 (25 hom., cov: 0)
  • Exomes 𝑓: 0.16 (18 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0543 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+23_4970+24delAA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+23_4970+24delAA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+23_4970+24delAA		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+8delAA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+7_4970+8delAA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+7_4325+8delAA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 1576 AN: 114210 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00676

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.00503

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.0194

GnomAD2 exomes AF: 0.191 AC: 16531 AN: 86686 AF XY: 0.194

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.155 AC: 114591 AN: 738752 Hom.: 18 AF XY: 0.157 AC XY: 59958 AN XY: 381412

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

African (AFR) AF: 0.169 AC: 2873 AN: 17038

American (AMR) AF: 0.171 AC: 3625 AN: 21228

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 2602 AN: 15624

East Asian (EAS) AF: 0.228 AC: 7083 AN: 31008

South Asian (SAS) AF: 0.159 AC: 7262 AN: 45794

European-Finnish (FIN) AF: 0.155 AC: 5585 AN: 35964

Middle Eastern (MID) AF: 0.168 AC: 426 AN: 2532

European-Non Finnish (NFE) AF: 0.149 AC: 79712 AN: 536380

Other (OTH) AF: 0.163 AC: 5423 AN: 33184

⚠️ 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: 0.0138 AC: 1579 AN: 114202 Hom.: 25 Cov.: 0 AF XY: 0.0150 AC XY: 821 AN XY: 54630

African (AFR) AF: 0.0122 AC: 372 AN: 30486

American (AMR) AF: 0.0178 AC: 204 AN: 11432

Ashkenazi Jewish (ASJ) AF: 0.00676 AC: 19 AN: 2812

East Asian (EAS) AF: 0.0602 AC: 272 AN: 4520

South Asian (SAS) AF: 0.0445 AC: 160 AN: 3596

European-Finnish (FIN) AF: 0.00503 AC: 28 AN: 5562

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.00910 AC: 485 AN: 53312

Other (OTH) AF: 0.0237 AC: 38 AN: 1602

Alfa AF: 0.000580 Hom.: 74

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;