1-221723183-C-G

Position:

• chr1-221723183-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

DUSP10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP10	NM_007207.6	c.811+15751G>C		intron_variant		ENST00000366899.4	NP_009138.1
DUSP10	NR_111939.2	n.58+13660G>C		intron_variant
DUSP10	NR_111940.2	n.110-16717G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP10	ENST00000366899.4	c.811+15751G>C		intron_variant		1	NM_007207.6	ENSP00000355866.3
DUSP10	ENST00000468085.5	n.-28+13660G>C		intron_variant		1		ENSP00000483812.1
DUSP10	ENST00000477026.5	n.-27-16717G>C		intron_variant		2		ENSP00000482935.1

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

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.336

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.40

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: rs12724393; hg19: chr1-221896525; COSMIC: COSV60457022;