rs116348108

Positions:

• chr5-119099432-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001290321.3(DMXL1):​c.213+1328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,210 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.022 (68 hom., cov: 32)
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3374/152210) while in subpopulation NFE AF= 0.038 (2587/67996). AF 95% confidence interval is 0.0368. There are 68 homozygotes in gnomad4. There are 1548 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 68 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1	NM_001290321.3	c.213+1328A>G		intron_variant		ENST00000539542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMXL1	ENST00000539542.6	c.213+1328A>G		intron_variant		1	NM_001290321.3	A1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3374 AN: 152092 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0222 AC: 3374 AN: 152210 Hom.: 68 Cov.: 32 AF XY: 0.0208 AC XY: 1548 AN XY: 74416

Gnomad4 AFR AF: 0.00599

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0322 Hom.: 17

Bravo AF: 0.0221

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.49

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: rs116348108; hg19: chr5-118435127;