Variant 1-159782276-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001319658.2(DUSP23):c.391G>T(p.Gly131Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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. G131S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DUSP23
NM_001319658.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.51

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:

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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, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DUSP23	NM_001319658.2 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	2/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	3/3		NP_001306588.1
DUSP23	NM_017823.5 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	3/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DUSP23	ENST00000368107.2 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	2/2	1	NM_001319658.2	ENSP00000357087	P1
DUSP23	ENST00000368108.7 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	3/3	1		ENSP00000357088	P1
DUSP23	ENST00000368109.5 linkuse as main transcript	c.391G>T	p.Gly131Cys	missense_variant	3/3	2		ENSP00000357089	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.7

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.4

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.80

MutPred

0.60

Loss of disorder (P = 0.0133);Loss of disorder (P = 0.0133);Loss of disorder (P = 0.0133);

MVP

0.82

MPC

1.1

ClinPred

1.0

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over