Variant 12-89351700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001946.4(DUSP6):c.340G>A(p.Val114Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000374 in 1,603,928 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V114L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DUSP6
NM_001946.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05

Variant links:

Genes affected

DUSP6 (HGNC:3072): (dual specificity phosphatase 6) 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 ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Mutations in this gene have been associated with congenital hypogonadotropic hypogonadism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

DUSP6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP6	NM_001946.4 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	1/3	ENST00000279488.8
DUSP6	NM_022652.4 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP6	ENST00000279488.8 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	1/3	1	NM_001946.4	P1	Q16828-1
DUSP6	ENST00000308385.6 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	1/2	1			Q16828-2
	ENST00000611513.1 linkuse as main transcript	n.686C>T		non_coding_transcript_exon_variant	1/1
DUSP6	ENST00000548755.1 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451922

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721512

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0000725

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.2

M;M;.

MutationTaster

Benign

9.6e-8

P;P

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.047

D;D;D

Sift4G

Benign

0.11

T;D;D

Polyphen

1.0

D;D;.

Vest4

0.52

MutPred

0.40

Gain of catalytic residue at S113 (P = 0);Gain of catalytic residue at S113 (P = 0);Gain of catalytic residue at S113 (P = 0);

MVP

0.53

MPC

1.3

ClinPred

0.97

GERP RS

5.1

Varity_R

0.48

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over