dbSNP rs1129923: DUSP23:p.Gly131Ser (chr1-159782276-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001319658.2(DUSP23):c.391G>A(p.Gly131Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,613,962 control chromosomes in the GnomAD database, including 7,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 528 hom., cov: 32)

Exomes 𝑓: 0.091 ( 6597 hom. )

Consequence

DUSP23
NM_001319658.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.51

Publications

29 publications found

Variant links:

Genes affected

DUSP23 (HGNC:21480): (dual specificity phosphatase 23) Enables protein tyrosine/serine/threonine phosphatase activity. Involved in dephosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DUSP23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019216537).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319658.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP23	NM_001319658.2	MANE Select	c.391G>A	p.Gly131Ser	missense	Exon 2 of 2	NP_001306587.1	A0A140VJI5
DUSP23	NM_001319659.2		c.391G>A	p.Gly131Ser	missense	Exon 3 of 3	NP_001306588.1	A0A140VJI5
DUSP23	NM_017823.5		c.391G>A	p.Gly131Ser	missense	Exon 3 of 3	NP_060293.2	Q9BVJ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP23	ENST00000368107.2	TSL:1 MANE Select	c.391G>A	p.Gly131Ser	missense	Exon 2 of 2	ENSP00000357087.1	Q9BVJ7
DUSP23	ENST00000368108.7	TSL:1	c.391G>A	p.Gly131Ser	missense	Exon 3 of 3	ENSP00000357088.3	Q9BVJ7
DUSP23	ENST00000880030.1		c.433G>A	p.Gly145Ser	missense	Exon 2 of 2	ENSP00000550089.1

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10910

AN:

151958

Hom.:

529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0962

Gnomad OTH

AF:

0.0762

GnomAD2 exomes

AF:

0.0848

AC:

21319

AN:

251476

AF XY:

0.0892

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.00446

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.0972

Gnomad OTH exome

AF:

0.0924

GnomAD4 exome

AF:

0.0910

AC:

133102

AN:

1461884

Hom.:

6597

Cov.:

AF XY:

0.0926

AC XY:

67341

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0138

AC:

461

AN:

33480

American (AMR)

AF:

0.0430

AC:

1925

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

3199

AN:

26134

East Asian (EAS)

AF:

0.00239

AC:

AN:

39700

South Asian (SAS)

AF:

0.123

AC:

10616

AN:

86258

European-Finnish (FIN)

AF:

0.135

AC:

7186

AN:

53418

Middle Eastern (MID)

AF:

0.0501

AC:

289

AN:

5768

European-Non Finnish (NFE)

AF:

0.0936

AC:

104099

AN:

1112006

Other (OTH)

AF:

0.0866

AC:

5232

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7305

14611

21916

29222

36527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3702

7404

11106

14808

18510

<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:

0.0717

AC:

10904

AN:

152078

Hom.:

528

Cov.:

AF XY:

0.0734

AC XY:

5459

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0150

AC:

624

AN:

41480

American (AMR)

AF:

0.0623

AC:

952

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

424

AN:

3470

East Asian (EAS)

AF:

0.00521

AC:

AN:

5178

South Asian (SAS)

AF:

0.129

AC:

621

AN:

4802

European-Finnish (FIN)

AF:

0.135

AC:

1431

AN:

10596

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0962

AC:

6540

AN:

67962

Other (OTH)

AF:

0.0754

AC:

159

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

504

1009

1513

2018

2522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0871

Hom.:

3029

Bravo

AF:

0.0619

TwinsUK

AF:

0.0949

AC:

352

ALSPAC

AF:

0.0848

AC:

327

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0921

AC:

792

ExAC

AF:

0.0850

AC:

10325

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.0972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

PhyloP100

9.5

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.27

Sift

Uncertain

0.013

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.47

MPC

1.1

ClinPred

0.020

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.80

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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