chr1-221722051-T-C

Variant names:

• chr1-221722051-T-C
• rs17010629
• NM_007207.6:c.812-15585A>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.812-15585A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,978 control chromosomes in the GnomAD database, including 17,244 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 0.47 (17244 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP10	NM_007207.6	c.812-15585A>G		intron_variant	Intron 2 of 3	ENST00000366899.4	NP_009138.1
DUSP10	NR_111939.2	n.58+14792A>G		intron_variant	Intron 1 of 2
DUSP10	NR_111940.2	n.110-15585A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP10	ENST00000366899.4	c.812-15585A>G		intron_variant	Intron 2 of 3	1	NM_007207.6	ENSP00000355866.3
DUSP10	ENST00000468085.5	n.-28+14792A>G		intron_variant	Intron 1 of 2	1		ENSP00000483812.1
DUSP10	ENST00000477026.5	n.-27-15585A>G		intron_variant	Intron 1 of 2	2		ENSP00000482935.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70834 AN: 151860 Hom.: 17241 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.466 AC: 70866 AN: 151978 Hom.: 17244 Cov.: 32 AF XY: 0.458 AC XY: 34030 AN XY: 74274

African (AFR) AF: 0.379 AC: 15707 AN: 41442

American (AMR) AF: 0.390 AC: 5966 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1556 AN: 5154

South Asian (SAS) AF: 0.377 AC: 1815 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4838 AN: 10570

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37259 AN: 67930

Other (OTH) AF: 0.491 AC: 1035 AN: 2108

Alfa AF: 0.517 Hom.: 83022

Bravo AF: 0.457

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.18
Mutation Taster		=96/4	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: rs17010629; hg19: chr1-221895393;