Variant 8-29340169-G-A 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_001394.7(DUSP4):c.508C>T(p.Pro170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DUSP4
NM_001394.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Variant links:

Genes affected

DUSP4 (HGNC:3070): (dual specificity phosphatase 4) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]

DUSP4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1168752).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP4	NM_001394.7 linkuse as main transcript	c.508C>T	p.Pro170Ser	missense_variant	2/4	ENST00000240100.7	NP_001385.1	Q13115-1
DUSP4	NM_057158.4 linkuse as main transcript	c.235C>T	p.Pro79Ser	missense_variant	3/5		NP_476499.1	Q13115-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP4	ENST00000240100.7 linkuse as main transcript	c.508C>T	p.Pro170Ser	missense_variant	2/4	1	NM_001394.7	ENSP00000240100.2		Q13115-1
DUSP4	ENST00000240101.2 linkuse as main transcript	c.235C>T	p.Pro79Ser	missense_variant	3/5	1		ENSP00000240101.2		Q13115-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246362

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133482

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:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460322

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726234

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

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 15, 2024

The c.508C>T (p.P170S) alteration is located in exon 2 (coding exon 2) of the DUSP4 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the proline (P) at amino acid position 170 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

L;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.026

Sift

Benign

0.032

D;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0040

B;.

Vest4

0.17

MutPred

0.29

Loss of sheet (P = 3e-04);.;

MVP

0.23

MPC

0.69

ClinPred

0.074

GERP RS

4.1

Varity_R

0.038

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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