22-30663578-TC-CT

Variant names:

• chr22-30663578-TC-CT
• NM_152511.5:c.425_426delGAinsAG
• DUSP18 p.Arg142Gln

Variant summary

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

The NM_152511.5(DUSP18):​c.425_426delGAinsAG​(p.Arg142Gln) variant causes a missense change. 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: DUSP18 NM_152511.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

Genes affected

DUSP18 (HGNC:18484): (dual specificity phosphatase 18) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP18 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152511.5. 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
	DUSP18	NM_152511.5	MANE Select	c.425_426delGAinsAG	p.Arg142Gln	missense	N/A	NP_689724.3
	DUSP18	NM_001304794.2		c.425_426delGAinsAG	p.Arg142Gln	missense	N/A	NP_001291723.1	Q8NEJ0
	DUSP18	NM_001304795.2		c.425_426delGAinsAG	p.Arg142Gln	missense	N/A	NP_001291724.1	Q8NEJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP18	ENST00000334679.4	TSL:1 MANE Select	c.425_426delGAinsAG	p.Arg142Gln	missense	N/A	ENSP00000333917.3	Q8NEJ0
	DUSP18	ENST00000404885.5	TSL:1	c.425_426delGAinsAG	p.Arg142Gln	missense	N/A	ENSP00000385463.1	Q8NEJ0
	DUSP18	ENST00000403268.1	TSL:1	c.315_316delGAinsAG	p.Thr106Ala	missense	N/A	ENSP00000384946.1	F2Z2P2

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		6.1

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: chr22-31059565;