rs1063179

Variant names:

• chr1-161752414-C-T
• rs1063179
• NM_007240.3:c.624C>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.624C>T​(p.Thr208Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,611,540 control chromosomes in the GnomAD database, including 7,077 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 0.14 (2700 hom., cov: 32)
  • Exomes 𝑓: 0.057 (4377 hom.)
• Consequence: DUSP12 NM_007240.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 17 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=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.021 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP12	NM_007240.3	c.624C>T	p.Thr208Thr	synonymous_variant	Exon 4 of 6	ENST00000367943.5	NP_009171.1
DUSP12	XM_005244862.4	c.234C>T	p.Thr78Thr	synonymous_variant	Exon 4 of 6		XP_005244919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP12	ENST00000367943.5	c.624C>T	p.Thr208Thr	synonymous_variant	Exon 4 of 6	1	NM_007240.3	ENSP00000356920.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20806 AN: 151942 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0748 AC: 18777 AN: 251170 AF XY: 0.0664

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.0365

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.0607

Gnomad NFE exome AF: 0.0441

Gnomad OTH exome AF: 0.0560

GnomAD4 exome AF: 0.0569 AC: 83087 AN: 1459480 Hom.: 4377 Cov.: 30 AF XY: 0.0552 AC XY: 40058 AN XY: 726158

African (AFR) AF: 0.341 AC: 11358 AN: 33324

American (AMR) AF: 0.0407 AC: 1819 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0356 AC: 928 AN: 26092

East Asian (EAS) AF: 0.161 AC: 6390 AN: 39626

South Asian (SAS) AF: 0.0249 AC: 2147 AN: 86092

European-Finnish (FIN) AF: 0.0578 AC: 3085 AN: 53360

Middle Eastern (MID) AF: 0.0370 AC: 213 AN: 5754

European-Non Finnish (NFE) AF: 0.0475 AC: 52698 AN: 1110308

Other (OTH) AF: 0.0738 AC: 4449 AN: 60264

GnomAD4 genome AF: 0.137 AC: 20845 AN: 152060 Hom.: 2700 Cov.: 32 AF XY: 0.134 AC XY: 9972 AN XY: 74328

African (AFR) AF: 0.339 AC: 14027 AN: 41430

American (AMR) AF: 0.0699 AC: 1069 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5182

South Asian (SAS) AF: 0.0291 AC: 140 AN: 4814

European-Finnish (FIN) AF: 0.0619 AC: 655 AN: 10574

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0508 AC: 3455 AN: 67986

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.0803 Hom.: 1222

Bravo AF: 0.148

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.28
PhyloP100		-0.021
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: rs1063179; hg19: chr1-161722204; COSMIC: COSV63411115; COSMIC: COSV63411115;