1-221723183-C-G

Variant names:

• chr1-221723183-C-G
• rs12724393
• NM_007207.6:c.811+15751G>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.811+15751G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,986 control chromosomes in the GnomAD database, including 8,563 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 0.33 (8563 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 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.811+15751G>C		intron	N/A	NP_009138.1	Q9Y6W6-1
	DUSP10	NR_111939.2		n.58+13660G>C		intron	N/A
	DUSP10	NR_111940.2		n.110-16717G>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.811+15751G>C		intron	N/A	ENSP00000355866.3	Q9Y6W6-1
	DUSP10	ENST00000468085.5	TSL:1	n.-28+13660G>C		intron	N/A	ENSP00000483812.1	A0A0B4J2F5
	DUSP10	ENST00000891852.1		c.811+15751G>C		intron	N/A	ENSP00000561911.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50031 AN: 151868 Hom.: 8557 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.329 AC: 50061 AN: 151986 Hom.: 8563 Cov.: 32 AF XY: 0.321 AC XY: 23817 AN XY: 74272

African (AFR) AF: 0.310 AC: 12831 AN: 41428

American (AMR) AF: 0.270 AC: 4129 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1378 AN: 3472

East Asian (EAS) AF: 0.132 AC: 681 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4816

European-Finnish (FIN) AF: 0.284 AC: 2997 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25594 AN: 67950

Other (OTH) AF: 0.336 AC: 707 AN: 2106

Alfa AF: 0.230 Hom.: 526

Bravo AF: 0.329

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.17
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: rs12724393; hg19: chr1-221896525; COSMIC: COSV60457022;