rs12126069

Variant names:

• chr1-221707509-A-G
• rs12126069
• NM_007207.6:c.812-1043T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007207.6(DUSP10):​c.812-1043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,028 control chromosomes in the GnomAD database, including 12,223 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 0.38 (12223 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 4 publications found

Genes affected

DUSP10 (HGNC:3065): (dual specificity phosphatase 10) Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the MAP kinase superfamily, which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity phosphatases show distinct substrate specificities for MAP kinases, different tissue distribution and subcellular localization, and different modes of expression induction by extracellular stimuli. This gene product binds to and inactivates p38 and SAPK/JNK. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007207.6. 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
	DUSP10	NM_007207.6	MANE Select	c.812-1043T>C		intron	N/A	NP_009138.1	Q9Y6W6-1
	DUSP10	NR_111939.2		n.59-1043T>C		intron	N/A
	DUSP10	NR_111940.2		n.110-1043T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP10	ENST00000366899.4	TSL:1 MANE Select	c.812-1043T>C		intron	N/A	ENSP00000355866.3	Q9Y6W6-1
	DUSP10	ENST00000468085.5	TSL:1	n.-27-1043T>C		intron	N/A	ENSP00000483812.1	A0A0B4J2F5
	DUSP10	ENST00000891852.1		c.812-1043T>C		intron	N/A	ENSP00000561911.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57060 AN: 151910 Hom.: 12221 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 57074 AN: 152028 Hom.: 12223 Cov.: 32 AF XY: 0.377 AC XY: 27997 AN XY: 74302

African (AFR) AF: 0.162 AC: 6738 AN: 41494

American (AMR) AF: 0.406 AC: 6197 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2277 AN: 5168

South Asian (SAS) AF: 0.560 AC: 2702 AN: 4828

European-Finnish (FIN) AF: 0.407 AC: 4292 AN: 10540

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31868 AN: 67942

Other (OTH) AF: 0.411 AC: 866 AN: 2106

Alfa AF: 0.409 Hom.: 2311

Bravo AF: 0.359

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Benign	0.76
PhyloP100		0.94
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: rs12126069; hg19: chr1-221880851;