Variant 1-221706188-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_007207.6(DUSP10):c.1090G>A(p.Glu364Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,894 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DUSP10
NM_007207.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

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 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=0.40630454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DUSP10	NM_007207.6 linkuse as main transcript	c.1090G>A	p.Glu364Lys	missense_variant	3/4	ENST00000366899.4
DUSP10	XM_047442948.1 linkuse as main transcript	c.307G>A	p.Glu103Lys	missense_variant	2/3
DUSP10	NR_111939.2 linkuse as main transcript	n.337G>A		non_coding_transcript_exon_variant	2/3
DUSP10	NR_111940.2 linkuse as main transcript	n.388G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP10	ENST00000366899.4 linkuse as main transcript	c.1090G>A	p.Glu364Lys	missense_variant	3/4	1	NM_007207.6	P1	Q9Y6W6-1
DUSP10	ENST00000468085.5 linkuse as main transcript	c.*51G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	1
DUSP10	ENST00000477026.5 linkuse as main transcript	c.*51G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	2
DUSP10	ENST00000494642.1 linkuse as main transcript	c.*51G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

Jun 03, 2022

The c.1090G>A (p.E364K) alteration is located in exon 3 (coding exon 2) of the DUSP10 gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the glutamic acid (E) at amino acid position 364 to be replaced by a lysine (K). 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

0.18

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0073

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.043

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.34

Sift

Benign

0.12

Sift4G

Benign

0.44

Polyphen

0.17

Vest4

0.58

MutPred

0.55

Gain of methylation at E364 (P = 0.0161);

MVP

0.88

MPC

0.44

ClinPred

0.90

GERP RS

4.5

Varity_R

0.58

gMVP

0.45

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