Variant X-44844701-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022076.4(DUSP21):c.569T>C(p.Met190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,078,059 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 4 hem. )

Consequence

DUSP21
NM_022076.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13170323).

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.569T>C	p.Met190Thr	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.569T>C	p.Met190Thr	missense_variant	1/1	6	NM_022076.4	ENSP00000343244.4		Q9H596

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000594

AC:

AN:

168225

Hom.:

AF XY:

0.00

AC XY:

AN XY:

55865

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:

0.0000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1078059

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

347949

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

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:

0.0000145

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 24, 2024

The c.569T>C (p.M190T) alteration is located in exon 1 (coding exon 1) of the DUSP21 gene. This alteration results from a T to C substitution at nucleotide position 569, causing the methionine (M) at amino acid position 190 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

0.16

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.5

DANN

Benign

0.58

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.19

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.030

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.26

Vest4

0.20

MutPred

0.48

Gain of catalytic residue at M190 (P = 0.061);

MVP

0.10

MPC

0.70

ClinPred

0.15

GERP RS

-0.55

Varity_R

0.32

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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