Genetic Variant DUSP10:p.Val419Phe (chr1-221702606-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007207.6(DUSP10):c.1255G>T(p.Val419Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. V419I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DUSP10
NM_007207.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17

Publications

0 publications found

Variant links:

Genes affected

DUSP10 (HGNC:3065): (dual specificity phosphatase 10) Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the MAP kinase superfamily, which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity phosphatases show distinct substrate specificities for MAP kinases, different tissue distribution and subcellular localization, and different modes of expression induction by extracellular stimuli. This gene product binds to and inactivates p38 and SAPK/JNK. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

DUSP10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007207.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP10	NM_007207.6	MANE Select	c.1255G>T	p.Val419Phe	missense	Exon 4 of 4	NP_009138.1	Q9Y6W6-1
DUSP10	NR_111939.2		n.502G>T		non_coding_transcript_exon	Exon 3 of 3
DUSP10	NR_111940.2		n.553G>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP10	ENST00000366899.4	TSL:1 MANE Select	c.1255G>T	p.Val419Phe	missense	Exon 4 of 4	ENSP00000355866.3	Q9Y6W6-1
DUSP10	ENST00000468085.5	TSL:1	n.*216G>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000483812.1	A0A0B4J2F5
DUSP10	ENST00000468085.5	TSL:1	n.*216G>T		3_prime_UTR	Exon 3 of 3	ENSP00000483812.1	A0A0B4J2F5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.5

PhyloP100

6.2

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.8

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.92

MutPred

0.79

Loss of MoRF binding (P = 0.0895)

MVP

0.95

MPC

1.3

ClinPred

0.98

GERP RS

5.7

Varity_R

0.85

gMVP

0.95

Mutation Taster

=6/94

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over