1-46510953-CGG-GGT

Variant names:

• chr1-46510953-CGG-GGT
• NM_172225.2:c.352_354delCGGinsGGT
• DMBX1 p.Arg118Gly

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_172225.2(DMBX1):​c.352_354delCGGinsGGT​(p.Arg118Gly) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R118W) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DMBX1 NM_172225.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

DMBX1 (HGNC:19026): (diencephalon/mesencephalon homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DMBX1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-46510953-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 183286.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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_172225.2. 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
	DMBX1	NM_172225.2	MANE Select	c.352_354delCGGinsGGT	p.Arg118Gly	missense	N/A	NP_757379.1	Q8NFW5-2
	DMBX1	NM_001387776.1		c.367_369delCGGinsGGT	p.Arg123Gly	missense	N/A	NP_001374705.1	Q8NFW5-1
	DMBX1	NM_147192.4		c.367_369delCGGinsGGT	p.Arg123Gly	missense	N/A	NP_671725.1	Q8NFW5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBX1	ENST00000360032.4	TSL:1 MANE Select	c.352_354delCGGinsGGT	p.Arg118Gly	missense	N/A	ENSP00000353132.3	Q8NFW5-2
	DMBX1	ENST00000928354.1		c.352_354delCGGinsGGT	p.Arg118Gly	missense	N/A	ENSP00000598413.1
	DMBX1	ENST00000928355.1		c.352_354delCGGinsGGT	p.Arg118Gly	missense	N/A	ENSP00000598414.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

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: chr1-46976625;