Genetic Variant NM_007240.3:c.68G>A (chr1-161749869-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007240.3(DUSP12):c.68G>A(p.Cys23Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. C23S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DUSP12
NM_007240.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.853

Variant links:

Genes affected

DUSP12 (HGNC:3067): (dual specificity phosphatase 12) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product is the human ortholog of the Saccharomyces cerevisiae YVH1 protein tyrosine phosphatase. It is localized predominantly in the nucleus, and is novel in that it contains, and is regulated by a zinc finger domain. [provided by RefSeq, Jul 2008]

DUSP12 links:

ATF6-DT (HGNC:55826): (ATF6 divergent transcript)

ATF6-DT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06683615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP12	NM_007240.3 link	c.68G>A	p.Cys23Tyr	missense_variant	Exon 1 of 6	ENST00000367943.5	NP_009171.1	Q9UNI6
DUSP12	XM_005244862.4 link	c.-336G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		XP_005244919.1
DUSP12	XM_005244862.4 link	c.-336G>A		5_prime_UTR_variant	Exon 1 of 6		XP_005244919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP12	ENST00000367943.5 link	c.68G>A	p.Cys23Tyr	missense_variant	Exon 1 of 6	1	NM_007240.3	ENSP00000356920.4		Q9UNI6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725412

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

DANN

Benign

0.74

DEOGEN2

Benign

0.083

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.40

M_CAP

Benign

0.0026

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.69

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.47

REVEL

Benign

0.023

Sift

Benign

0.048

Sift4G

Uncertain

0.033

Polyphen

0.14

Vest4

0.29

MutPred

0.33

Gain of phosphorylation at C23 (P = 0.0148);

MVP

0.14

MPC

0.51

ClinPred

0.80

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over