Variant chrX-44844145-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022076.4(DUSP21):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,206,785 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000014 ( 0 hom. 4 hem. )

Consequence

DUSP21
NM_022076.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

Variant links:

Genes affected

DUSP21 (HGNC:20476): (dual specificity phosphatase 21) This gene encodes a member of the dual specificity phosphatase family, specifically the low molecular weight dual specificity phosphatase family. The encoded protein localizes to both the cytoplasm and the nucleus and functions to remove phosphate groups from phosphotyrosine and phosphothreonine residues.[provided by RefSeq, Mar 2009]

DUSP21 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=0.041542113).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP21	NM_022076.4 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/1	ENST00000339042.6	NP_071359.3	Q9H596

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP21	ENST00000339042.6 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/1	6	NM_022076.4	ENSP00000343244.4		Q9H596

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33784

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

178190

Hom.:

AF XY:

0.0000317

AC XY:

AN XY:

63046

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:

0.0000251

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1095173

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361001

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:

0.0000178

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33784

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:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

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

Sep 26, 2024

The c.13G>A (p.A5T) alteration is located in exon 1 (coding exon 1) of the DUSP21 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 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

Benign

0.088

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.96

DANN

Benign

0.71

DEOGEN2

Benign

0.0084

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.23

M_CAP

Benign

0.0026

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.2

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.10

REVEL

Benign

0.025

Sift

Benign

0.37

Sift4G

Benign

0.49

Polyphen

0.024

Vest4

0.019

MutPred

0.17

Gain of glycosylation at A5 (P = 0.0135);

MVP

0.45

MPC

0.54

ClinPred

0.038

GERP RS

-3.2

Varity_R

0.050

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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