1-221706244-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007207.6(DUSP10):c.1034G>A(p.Arg345Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DUSP10
NM_007207.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25727597).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP10	NM_007207.6 link	c.1034G>A	p.Arg345Gln	missense_variant	Exon 3 of 4	ENST00000366899.4	NP_009138.1	Q9Y6W6-1
DUSP10	XM_047442948.1 link	c.251G>A	p.Arg84Gln	missense_variant	Exon 2 of 3		XP_047298904.1
DUSP10	NR_111939.2 link	n.281G>A		non_coding_transcript_exon_variant	Exon 2 of 3
DUSP10	NR_111940.2 link	n.332G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUSP10	ENST00000366899.4 link	c.1034G>A	p.Arg345Gln	missense_variant	Exon 3 of 4	1	NM_007207.6	ENSP00000355866.3	Q9Y6W6-1
DUSP10	ENST00000468085.5 link	n.196G>A		non_coding_transcript_exon_variant	Exon 2 of 3	1		ENSP00000483812.1	A0A0B4J2F5
DUSP10	ENST00000477026.5 link	n.196G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000482935.1	A0A0B4J2F5
DUSP10	ENST00000494642.1 link	n.196G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000480008.1	A0A0B4J2F5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

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

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251480

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000688

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:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1034G>A (p.R345Q) 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 1034, causing the arginine (R) at amino acid position 345 to be replaced by a glutamine (Q). 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

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.023

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.80

M_CAP

Benign

0.020

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.35

REVEL

Benign

0.12

Sift

Benign

0.24

Sift4G

Benign

0.61

Polyphen

0.92

Vest4

0.42

MVP

0.67

MPC

0.88

ClinPred

0.17

GERP RS

4.4

Varity_R

0.30

gMVP

0.50

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