Variant chr1-159781120-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001319658.2(DUSP23):c.20A>C(p.Asn7Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,546,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

DUSP23
NM_001319658.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.29

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2 linkuse as main transcript	c.20A>C	p.Asn7Thr	missense_variant	1/2	ENST00000368107.2	NP_001306587.1	Q9BVJ7A0A140VJI5
DUSP23	NM_001319659.2 linkuse as main transcript	c.20A>C	p.Asn7Thr	missense_variant	2/3		NP_001306588.1	Q9BVJ7A0A140VJI5
DUSP23	NM_017823.5 linkuse as main transcript	c.20A>C	p.Asn7Thr	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.20A>C	p.Asn7Thr	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1	Q9BVJ7
DUSP23	ENST00000368108.7 linkuse as main transcript	c.20A>C	p.Asn7Thr	missense_variant	2/3	1		ENSP00000357088.3	Q9BVJ7
DUSP23	ENST00000368109.5 linkuse as main transcript	c.20A>C	p.Asn7Thr	missense_variant	2/3	2		ENSP00000357089.1	Q9BVJ7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000574

AC:

AN:

1394582

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688066

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:

0.00000742

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

May 26, 2024

The c.20A>C (p.N7T) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a A to C substitution at nucleotide position 20, causing the asparagine (N) at amino acid position 7 to be replaced by a threonine (T). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

.;.;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

M;M;M

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.020

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.70

MutPred

0.53

Gain of glycosylation at N7 (P = 0.0279);Gain of glycosylation at N7 (P = 0.0279);Gain of glycosylation at N7 (P = 0.0279);

MVP

0.67

MPC

1.0

ClinPred

1.0

GERP RS

4.9

Varity_R

0.77

gMVP

0.76

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

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