dbSNP rs1251831323: DUSP18:p.Arg142Pro (chr22-30663579-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152511.5(DUSP18):c.425G>C(p.Arg142Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R142Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DUSP18
NM_152511.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.08

Variant links:

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]

DUSP18 links:

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]

SLC35E4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP18	NM_152511.5 link	c.425G>C	p.Arg142Pro	missense_variant	Exon 2 of 2	ENST00000334679.4	NP_689724.3	Q8NEJ0A0A024R1L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP18	ENST00000334679.4 link	c.425G>C	p.Arg142Pro	missense_variant	Exon 2 of 2	1	NM_152511.5	ENSP00000333917.3		Q8NEJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;D;D;.

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

.;.;T;T

M_CAP

Uncertain

0.096

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Pathogenic

3.1

M;M;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.4

D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.88

MutPred

0.64

Loss of MoRF binding (P = 0.0471);Loss of MoRF binding (P = 0.0471);Loss of MoRF binding (P = 0.0471);Loss of MoRF binding (P = 0.0471);

MVP

0.90

MPC

0.14

ClinPred

0.99

GERP RS

5.3

Varity_R

0.88

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over