Genetic Variant DUSP28:p.Ser110Leu (chr2-240561013-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001370465.2(DUSP28):c.329C>T(p.Ser110Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000358 in 1,534,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DUSP28
NM_001370465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

Publications

0 publications found

Variant links:

Genes affected

DUSP28 (HGNC:33237): (dual specificity phosphatase 28) Enables phosphatase activity. Involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

DUSP28 links:

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKMY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370465.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP28	NM_001370465.2	MANE Select	c.329C>T	p.Ser110Leu	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
DUSP28	NM_001033575.1		c.329C>T	p.Ser110Leu	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2
ANKMY1	NM_001308375.4		c.-63G>A		5_prime_UTR	Exon 1 of 15	NP_001295304.3	J3KPY5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.329C>T	p.Ser110Leu	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
ANKMY1	ENST00000403283.6	TSL:1	c.-63G>A		5_prime_UTR	Exon 1 of 15	ENSP00000383968.1	J3KPY5
ANKMY1	ENST00000464991.5	TSL:1	n.433G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000654

AC:

AN:

137616

AF XY:

0.0000762

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:

0.0000494

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000347

AC:

AN:

1381894

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

684604

show subpopulations

African (AFR)

AF:

0.000167

AC:

AN:

29932

American (AMR)

AF:

0.0000300

AC:

AN:

33360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24048

East Asian (EAS)

AF:

0.00

AC:

AN:

35666

South Asian (SAS)

AF:

0.000278

AC:

AN:

79022

European-Finnish (FIN)

AF:

0.0000292

AC:

AN:

34216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3986

European-Non Finnish (NFE)

AF:

0.0000175

AC:

AN:

1084370

Other (OTH)

AF:

0.00

AC:

AN:

57294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41580

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000457

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.87

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

4.6

PhyloP100

5.5

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.7

REVEL

Pathogenic

0.90

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.81

MutPred

0.89

Loss of catalytic residue at S110 (P = 0.0541)

MVP

0.91

MPC

1.0

ClinPred

0.99

GERP RS

3.7

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.95

gMVP

0.87

Mutation Taster

=217/83

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over