chr5-119165286-TAAAAA-T

Variant names:

• chr5-119165286-TAAAAA-T
• rs11301800
• NM_001290321.3:c.4970+20_4970+24delAAAAA

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+11delAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00446 in 878,316 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: 𝑓 0.000026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (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: Variant has high frequency in the SAS (0.0095) population. However there is too low homozygotes in high coverage region: (expected more than 4, got 0).

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+20_4970+24delAAAAA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+20_4970+24delAAAAA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+20_4970+24delAAAAA		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+11delAAAAA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+7_4970+11delAAAAA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+7_4325+11delAAAAA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 3 AN: 114276 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000328

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: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00729 AC: 632 AN: 86686 AF XY: 0.00730

Gnomad AFR exome AF: 0.00446

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00572

Gnomad EAS exome AF: 0.0118

Gnomad FIN exome AF: 0.00353

Gnomad NFE exome AF: 0.00522

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00512 AC: 3914 AN: 764040 Hom.: 0 AF XY: 0.00518 AC XY: 2050 AN XY: 395454

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

African (AFR) AF: 0.00498 AC: 88 AN: 17688

American (AMR) AF: 0.0101 AC: 223 AN: 21988

Ashkenazi Jewish (ASJ) AF: 0.00504 AC: 83 AN: 16452

East Asian (EAS) AF: 0.00777 AC: 247 AN: 31774

South Asian (SAS) AF: 0.0103 AC: 486 AN: 47396

European-Finnish (FIN) AF: 0.00470 AC: 177 AN: 37668

Middle Eastern (MID) AF: 0.00381 AC: 10 AN: 2626

European-Non Finnish (NFE) AF: 0.00436 AC: 2414 AN: 553974

Other (OTH) AF: 0.00540 AC: 186 AN: 34474

⚠️ 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: 0.0000263 AC: 3 AN: 114276 Hom.: 0 Cov.: 0 AF XY: 0.0000366 AC XY: 2 AN XY: 54654

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

African (AFR) AF: 0.0000328 AC: 1 AN: 30460

American (AMR) AF: 0.00 AC: 0 AN: 11426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2814

East Asian (EAS) AF: 0.00 AC: 0 AN: 4542

South Asian (SAS) AF: 0.00 AC: 0 AN: 3622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000375 AC: 2 AN: 53338

Other (OTH) AF: 0.00 AC: 0 AN: 1598

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=98/2	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;