Variant 10-75043968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001003892.3(DUSP29):c.250G>A(p.Val84Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,613,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

DUSP29
NM_001003892.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

DUSP29 (HGNC:23481): (dual specificity phosphatase 29) Enables protein homodimerization activity and protein tyrosine/serine/threonine phosphatase activity. Involved in protein dephosphorylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

DUSP29 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3840759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP29	NM_001003892.3 linkuse as main transcript	c.250G>A	p.Val84Met	missense_variant	3/4	ENST00000338487.6	NP_001003892.1
DUSP29	NM_001384909.1 linkuse as main transcript	c.250G>A	p.Val84Met	missense_variant	4/5		NP_001371838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP29	ENST00000338487.6 linkuse as main transcript	c.250G>A	p.Val84Met	missense_variant	3/4	1	NM_001003892.3	ENSP00000340609	P1
	ENST00000649504.1 linkuse as main transcript	n.91+2002C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000196

AC:

AN:

249668

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.000124

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:

0.000418

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000361

AC:

528

AN:

1460776

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

262

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.0000564

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000236

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000721

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:

0.000470

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000316

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

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

Dec 05, 2022

The c.250G>A (p.V84M) alteration is located in exon 2 (coding exon 2) of the DUPD1 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the valine (V) at amino acid position 84 to be replaced by a methionine (M). 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

0.74

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Benign

0.56

M_CAP

Benign

0.074

MetaRNN

Benign

0.38

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

4.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.41

MVP

0.73

MPC

1.1

ClinPred

0.87

GERP RS

3.0

Varity_R

0.79

gMVP

0.65

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