1-221702677-T-G

Position:

chr1-221702677-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_007207.6(DUSP10):c.1184A>C(p.Glu395Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

DUSP10
NM_007207.6 missense, splice_region

Scores

Splicing: ADA: 0.002268

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DUSP10	NM_007207.6 linkuse as main transcript	c.1184A>C	p.Glu395Ala	missense_variant, splice_region_variant	4/4	ENST00000366899.4
DUSP10	XM_047442948.1 linkuse as main transcript	c.401A>C	p.Glu134Ala	missense_variant, splice_region_variant	3/3
DUSP10	NR_111939.2 linkuse as main transcript	n.431A>C		splice_region_variant, non_coding_transcript_exon_variant	3/3
DUSP10	NR_111940.2 linkuse as main transcript	n.482A>C		splice_region_variant, non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP10	ENST00000366899.4 linkuse as main transcript	c.1184A>C	p.Glu395Ala	missense_variant, splice_region_variant	4/4	1	NM_007207.6	P1	Q9Y6W6-1
DUSP10	ENST00000468085.5 linkuse as main transcript	c.*145A>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	3/3	1
DUSP10	ENST00000477026.5 linkuse as main transcript	c.*145A>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	3/3	2
DUSP10	ENST00000494642.1 linkuse as main transcript	c.*145A>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249560

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134934

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458792

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725598

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:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Oct 06, 2022

The c.1184A>C (p.E395A) alteration is located in exon 4 (coding exon 3) of the DUSP10 gene. This alteration results from a A to C substitution at nucleotide position 1184, causing the glutamic acid (E) at amino acid position 395 to be replaced by an alanine (A). 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.55

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.022

Polyphen

0.99

Vest4

0.66

MutPred

0.61

Loss of disorder (P = 0.1175);

MVP

0.88

MPC

1.1

ClinPred

0.97

GERP RS

4.6

Varity_R

0.78

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0023

dbscSNV1_RF

Benign

0.10

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