NM_007240.3:c.510C>T

Variant names:

• chr1-161751917-C-T
• rs1063178
• NM_007240.3:c.510C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007240.3(DUSP12):​c.510C>T​(p.Tyr170Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,609,770 control chromosomes in the GnomAD database, including 93,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9292 hom., cov: 32)
  • Exomes 𝑓: 0.34 (84393 hom.)
• Consequence: DUSP12 NM_007240.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 24 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.575 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP12	NM_007240.3	MANE Select	c.510C>T	p.Tyr170Tyr	synonymous	Exon 3 of 6	NP_009171.1	Q9UNI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP12	ENST00000367943.5	TSL:1 MANE Select	c.510C>T	p.Tyr170Tyr	synonymous	Exon 3 of 6	ENSP00000356920.4	Q9UNI6
	DUSP12	ENST00000931531.1		c.627C>T	p.Tyr209Tyr	synonymous	Exon 4 of 7	ENSP00000601590.1
	DUSP12	ENST00000954828.1		c.543C>T	p.Tyr181Tyr	synonymous	Exon 4 of 7	ENSP00000624887.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52696 AN: 151800 Hom.: 9287 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.335 AC: 84034 AN: 250490 AF XY: 0.338

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.476

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.337 AC: 490801 AN: 1457852 Hom.: 84393 Cov.: 35 AF XY: 0.338 AC XY: 244874 AN XY: 725348

African (AFR) AF: 0.388 AC: 12929 AN: 33348

American (AMR) AF: 0.248 AC: 11070 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8444 AN: 26056

East Asian (EAS) AF: 0.497 AC: 19723 AN: 39664

South Asian (SAS) AF: 0.344 AC: 29515 AN: 85860

European-Finnish (FIN) AF: 0.303 AC: 16184 AN: 53342

Middle Eastern (MID) AF: 0.401 AC: 2280 AN: 5682

European-Non Finnish (NFE) AF: 0.334 AC: 370393 AN: 1109096

Other (OTH) AF: 0.336 AC: 20263 AN: 60252

GnomAD4 genome AF: 0.347 AC: 52724 AN: 151918 Hom.: 9292 Cov.: 32 AF XY: 0.347 AC XY: 25751 AN XY: 74228

African (AFR) AF: 0.385 AC: 15943 AN: 41426

American (AMR) AF: 0.294 AC: 4476 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2485 AN: 5166

South Asian (SAS) AF: 0.359 AC: 1725 AN: 4806

European-Finnish (FIN) AF: 0.312 AC: 3279 AN: 10512

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22575 AN: 67970

Other (OTH) AF: 0.342 AC: 724 AN: 2114

Alfa AF: 0.339 Hom.: 39172

Bravo AF: 0.346

Asia WGS AF: 0.381 AC: 1323 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.3
DANN	Benign	0.46
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1063178; hg19: chr1-161721707; COSMIC: COSV63411078; COSMIC: COSV63411078;