5-119165286-TAAAA-T

Position:

• chr5-119165286-TAAAA-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001290321.3(DMXL1):​c.4970+21_4970+24del variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0174 in 867,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 hom., cov: 0)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: DMXL1 NM_001290321.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.02 (15087/752968) while in subpopulation AMR AF= 0.0364 (787/21614). AF 95% confidence interval is 0.0343. There are 0 homozygotes in gnomad4_exome. There are 7946 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1	NM_001290321.3	c.4970+21_4970+24del		splice_region_variant, intron_variant		ENST00000539542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMXL1	ENST00000539542.6	c.4970+21_4970+24del		splice_region_variant, intron_variant		1	NM_001290321.3	A1
DMXL1	ENST00000311085.8	c.4970+21_4970+24del		splice_region_variant, intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 9 AN: 114274 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000175

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000359

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000750

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0256 AC: 2222 AN: 86686 Hom.: 0 AF XY: 0.0263 AC XY: 1251 AN XY: 47508

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.0365

Gnomad SAS exome AF: 0.0413

Gnomad FIN exome AF: 0.00876

Gnomad NFE exome AF: 0.0193

Gnomad OTH exome AF: 0.0281

GnomAD4 exome AF: 0.0200 AC: 15087 AN: 752968 Hom.: 0 AF XY: 0.0204 AC XY: 7946 AN XY: 389448

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.0364

Gnomad4 ASJ exome AF: 0.0219

Gnomad4 EAS exome AF: 0.0314

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0224

GnomAD4 genome AF: 0.0000788 AC: 9 AN: 114266 Hom.: 0 Cov.: 0 AF XY: 0.0000732 AC XY: 4 AN XY: 54666

Gnomad4 AFR AF: 0.0000328

Gnomad4 AMR AF: 0.000175

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000359

Gnomad4 NFE AF: 0.0000750

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11301800; hg19: chr5-118500981;