rs116348108

Variant names:

• chr5-119099432-A-G
• rs116348108
• NM_001290321.3:c.213+1328A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 68 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.213+1328A>G		intron_variant	Intron 2 of 43	ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMXL1	ENST00000539542.6	c.213+1328A>G		intron_variant	Intron 2 of 43	1	NM_001290321.3	ENSP00000439479.1

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

African (AFR) AF: 0.00599 AC: 249 AN: 41550

American (AMR) AF: 0.0152 AC: 232 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0380 AC: 2587 AN: 67996

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0239 Hom.: 33

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
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116348108; hg19: chr5-118435127;