rs1063178

chr1-161751917-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007240.3(DUSP12):c.510C>T(p.Tyr170=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP12	NM_007240.3	c.510C>T	p.Tyr170=	synonymous_variant	3/6	ENST00000367943.5
DUSP12	XM_005244862.4	c.120C>T	p.Tyr40=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP12	ENST00000367943.5	c.510C>T	p.Tyr170=	synonymous_variant	3/6	1	NM_007240.3	P1
ATF6-DT	ENST00000702792.1	n.373-1550G>A		intron_variant, non_coding_transcript_variant
DUSP12	ENST00000464004.2	c.*109C>T		3_prime_UTR_variant, NMD_transcript_variant	3/5	2
DUSP12	ENST00000484291.5	c.*57+136C>T		intron_variant, NMD_transcript_variant		5

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

GnomAD3 exomes AF: 0.335 AC: 84034 AN: 250490 Hom.: 14682 AF XY: 0.338 AC XY: 45739 AN XY: 135410

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 SAS exome AF: 0.341

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

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.497

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.336

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.342

Alfa AF: 0.336 Hom.: 19748

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.3
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

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