Variant chrX-153648006-C-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_001318503.2(DUSP9):c.53C>A(p.Pro18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000404 in 988,958 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000040 ( 0 hom. 2 hem. )

Consequence

DUSP9
NM_001318503.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.594

Variant links:

Genes affected

DUSP9 (HGNC:3076): (dual specificity phosphatase 9) 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 is 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 shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DUSP9 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=0.1703935).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DUSP9	NM_001318503.2 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	2/4	ENST00000342782.4
DUSP9	NM_001395.4 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	2/4
DUSP9	XM_011531123.2 linkuse as main transcript	c.146C>A	p.Pro49Gln	missense_variant	2/4
DUSP9	XM_047441899.1 linkuse as main transcript	c.119C>A	p.Pro40Gln	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DUSP9	ENST00000342782.4 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	2/4	1	NM_001318503.2	P1
DUSP9	ENST00000370167.8 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	2/4	1		P1
DUSP9	ENST00000477033.1 linkuse as main transcript	n.423C>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000681

AC:

AN:

44044

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

9862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000285

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000404

AC:

AN:

988958

Hom.:

Cov.:

AF XY:

0.00000635

AC XY:

AN XY:

315208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000198

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

Cov.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.11

T;T

FATHMM_MKL

Benign

0.57

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.081

Sift

Benign

0.31

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.35

B;B

Vest4

0.18

MutPred

0.28

Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);

MVP

0.59

MPC

0.72

ClinPred

0.080

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.10

gMVP

0.16

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