Variant chr1-159781200-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001319658.2(DUSP23):c.100C>G(p.Leu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,549,534 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 18 hom. )

Consequence

DUSP23
NM_001319658.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.521

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053390265).

BS2

High Homozygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	1/2	ENST00000368107.2	NP_001306587.1	Q9BVJ7A0A140VJI5
DUSP23	NM_001319659.2 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	2/3		NP_001306588.1	Q9BVJ7A0A140VJI5
DUSP23	NM_017823.5 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	2/3		NP_060293.2	Q9BVJ7A0A140VJI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUSP23	ENST00000368107.2 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1	Q9BVJ7
DUSP23	ENST00000368108.7 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	2/3	1		ENSP00000357088.3	Q9BVJ7
DUSP23	ENST00000368109.5 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	2/3	2		ENSP00000357089.1	Q9BVJ7

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00586

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00266

AC:

378

AN:

142208

Hom.:

AF XY:

0.00254

AC XY:

194

AN XY:

76520

show subpopulations

Gnomad AFR exome

AF:

0.000879

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.000367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00138

Gnomad FIN exome

AF:

0.000334

Gnomad NFE exome

AF:

0.00529

Gnomad OTH exome

AF:

0.00290

GnomAD4 exome

AF:

0.00517

AC:

7219

AN:

1397170

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

3366

AN XY:

689064

show subpopulations

Gnomad4 AFR exome

AF:

0.000951

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.000358

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.000478

Gnomad4 NFE exome

AF:

0.00617

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152364

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00586

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00476

Hom.:

Bravo

AF:

0.00329

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00354

AC:

ExAC

AF:

0.000697

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.100C>G (p.L34V) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a C to G substitution at nucleotide position 100, causing the leucine (L) at amino acid position 34 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.050

T;T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.76

.;.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.070

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.071

MVP

0.28

MPC

0.34

ClinPred

0.0029

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.42

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over