Genetic Variant DUSP21:p.Leu184Val (chrX-44844682-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022076.4(DUSP21):c.550C>G(p.Leu184Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,201,568 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000075 ( 0 hom. 31 hem. )

Consequence

DUSP21
NM_022076.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.115

Publications

0 publications found

Variant links:

Genes affected

DUSP21 (HGNC:20476): (dual specificity phosphatase 21) This gene encodes a member of the dual specificity phosphatase family, specifically the low molecular weight dual specificity phosphatase family. The encoded protein localizes to both the cytoplasm and the nucleus and functions to remove phosphate groups from phosphotyrosine and phosphothreonine residues.[provided by RefSeq, Mar 2009]

DUSP21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024568677).

BP6

Variant X-44844682-C-G is Benign according to our data. Variant chrX-44844682-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2549116.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 31 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022076.4. 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
	DUSP21	NM_022076.4	MANE Select	c.550C>G	p.Leu184Val	missense	Exon 1 of 1	NP_071359.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP21	ENST00000339042.6	TSL:6 MANE Select	c.550C>G	p.Leu184Val	missense	Exon 1 of 1	ENSP00000343244.4	Q9H596

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110664

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000755

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

175820

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000382

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000752

AC:

AN:

1090904

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

357136

show subpopulations

African (AFR)

AF:

0.0000760

AC:

AN:

26300

American (AMR)

AF:

0.00

AC:

AN:

34820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18866

East Asian (EAS)

AF:

0.00

AC:

AN:

30142

South Asian (SAS)

AF:

0.00

AC:

AN:

52745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40307

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.0000943

AC:

AN:

837815

Other (OTH)

AF:

0.0000218

AC:

AN:

45806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30322

American (AMR)

AF:

0.00

AC:

AN:

10231

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2623

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

52979

Other (OTH)

AF:

0.00

AC:

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0020

(source)

DANN

Benign

0.10

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.35

M_CAP

Benign

0.0022

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.81

PhyloP100

-0.12

PrimateAI

Benign

0.34

PROVEAN

Benign

1.2

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.048

MutPred

0.31

Loss of catalytic residue at L184 (P = 0.0651)

MVP

0.35

MPC

0.57

ClinPred

0.034

GERP RS

-5.3

Varity_R

0.042

gMVP

0.78

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over