Variant 17-37512765-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007026.4(DUSP14):c.493C>G(p.Leu165Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DUSP14
NM_007026.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

DUSP14 (HGNC:17007): (dual specificity phosphatase 14) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP14 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

DUSP14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DUSP14	NM_007026.4 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3	ENST00000617516.5
DUSP14	XM_005256977.4 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3
DUSP14	XM_011524234.2 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3
DUSP14	XM_047435217.1 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DUSP14	ENST00000617516.5 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3	1	NM_007026.4	P1
DUSP14	ENST00000613659.1 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	3/3	2		P1
DUSP14	ENST00000614411.1 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727092

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 17, 2022

The c.493C>G (p.L165V) alteration is located in exon 3 (coding exon 1) of the DUSP14 gene. This alteration results from a C to G substitution at nucleotide position 493, causing the leucine (L) at amino acid position 165 to be replaced by a valine (V). 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

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.62

D;D;D

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.49

P;P;P

Vest4

0.69

MutPred

0.59

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.54

ClinPred

1.0

GERP RS

6.0

Varity_R

0.46

gMVP

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over