Variant 1-159782181-T-G 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.296T>G(p.Phe99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DUSP23
NM_001319658.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.968

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 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.296T>G	p.Phe99Cys	missense_variant	2/2	ENST00000368107.2	NP_001306587.1	Q9BVJ7A0A140VJI5
DUSP23	NM_001319659.2 linkuse as main transcript	c.296T>G	p.Phe99Cys	missense_variant	3/3		NP_001306588.1	Q9BVJ7A0A140VJI5
DUSP23	NM_017823.5 linkuse as main transcript	c.296T>G	p.Phe99Cys	missense_variant	3/3		NP_060293.2	Q9BVJ7A0A140VJI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUSP23	ENST00000368107.2 linkuse as main transcript	c.296T>G	p.Phe99Cys	missense_variant	2/2	1	NM_001319658.2	ENSP00000357087.1	Q9BVJ7
DUSP23	ENST00000368108.7 linkuse as main transcript	c.296T>G	p.Phe99Cys	missense_variant	3/3	1		ENSP00000357088.3	Q9BVJ7
DUSP23	ENST00000368109.5 linkuse as main transcript	c.296T>G	p.Phe99Cys	missense_variant	3/3	2		ENSP00000357089.1	Q9BVJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251298

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Mar 29, 2022

The c.296T>G (p.F99C) alteration is located in exon 3 (coding exon 2) of the DUSP23 gene. This alteration results from a T to G substitution at nucleotide position 296, causing the phenylalanine (F) at amino acid position 99 to be replaced by a cysteine (C). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.97

.;.;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.38

MutPred

0.66

Gain of methylation at R101 (P = 0.1128);Gain of methylation at R101 (P = 0.1128);Gain of methylation at R101 (P = 0.1128);

MVP

0.98

MPC

1.1

ClinPred

0.68

GERP RS

1.9

Varity_R

0.61

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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