5-119116288-GA-AG

Variant names:

• chr5-119116288-GA-AG
• NM_001290321.3:c.695_696delGAinsAG
• DMXL1 p.Arg232Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001290321.3(DMXL1):​c.695_696delGAinsAG​(p.Arg232Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMXL1 NM_001290321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.46
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290321.3. 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.695_696delGAinsAG	p.Arg232Gln	missense	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.695_696delGAinsAG	p.Arg232Gln	missense	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.695_696delGAinsAG	p.Arg232Gln	missense	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.695_696delGAinsAG	p.Arg232Gln	missense	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.695_696delGAinsAG	p.Arg232Gln	missense	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000503802.5	TSL:1	c.695_696delGAinsAG	p.Arg232Gln	missense	N/A	ENSP00000427692.1	E7EMZ0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-118451983;