1-221724004-A-C

Variant names:

• chr1-221724004-A-C
• rs11118838
• NM_007207.6:c.811+14930T>G

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+14930T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,120 control chromosomes in the GnomAD database, including 14,836 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 0.41 (14836 hom., cov: 33)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP10	NM_007207.6	MANE Select	c.811+14930T>G		intron	N/A	NP_009138.1
	DUSP10	NR_111939.2		n.58+12839T>G		intron	N/A
	DUSP10	NR_111940.2		n.110-17538T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP10	ENST00000366899.4	TSL:1 MANE Select	c.811+14930T>G		intron	N/A	ENSP00000355866.3
	DUSP10	ENST00000468085.5	TSL:1	n.-28+12839T>G		intron	N/A	ENSP00000483812.1
	DUSP10	ENST00000477026.5	TSL:2	n.-27-17538T>G		intron	N/A	ENSP00000482935.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62724 AN: 152002 Hom.: 14844 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.412 AC: 62721 AN: 152120 Hom.: 14836 Cov.: 33 AF XY: 0.406 AC XY: 30238 AN XY: 74404

African (AFR) AF: 0.191 AC: 7909 AN: 41488

American (AMR) AF: 0.372 AC: 5690 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1560 AN: 5180

South Asian (SAS) AF: 0.377 AC: 1820 AN: 4822

European-Finnish (FIN) AF: 0.457 AC: 4843 AN: 10590

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37246 AN: 67984

Other (OTH) AF: 0.460 AC: 969 AN: 2106

Alfa AF: 0.374 Hom.: 1707

Bravo AF: 0.396

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		-0.90
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: rs11118838; hg19: chr1-221897346; COSMIC: COSV60457028;