1-221709883-C-T

Variant names:

• chr1-221709883-C-T
• rs908858
• NM_007207.6:c.812-3417G>A

Variant summary

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

The NM_007207.6(DUSP10):​c.812-3417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,928 control chromosomes in the GnomAD database, including 25,278 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 0.58 (25278 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 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.812-3417G>A		intron	N/A	NP_009138.1
	DUSP10	NR_111939.2		n.59-3417G>A		intron	N/A
	DUSP10	NR_111940.2		n.110-3417G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP10	ENST00000366899.4	TSL:1 MANE Select	c.812-3417G>A		intron	N/A	ENSP00000355866.3
	DUSP10	ENST00000468085.5	TSL:1	n.-27-3417G>A		intron	N/A	ENSP00000483812.1
	DUSP10	ENST00000477026.5	TSL:2	n.-27-3417G>A		intron	N/A	ENSP00000482935.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87307 AN: 151806 Hom.: 25254 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.575 AC: 87381 AN: 151928 Hom.: 25278 Cov.: 32 AF XY: 0.575 AC XY: 42676 AN XY: 74236

African (AFR) AF: 0.586 AC: 24279 AN: 41416

American (AMR) AF: 0.524 AC: 8004 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3466

East Asian (EAS) AF: 0.501 AC: 2592 AN: 5174

South Asian (SAS) AF: 0.663 AC: 3193 AN: 4814

European-Finnish (FIN) AF: 0.599 AC: 6305 AN: 10534

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39155 AN: 67940

Other (OTH) AF: 0.585 AC: 1233 AN: 2108

Alfa AF: 0.578 Hom.: 28057

Bravo AF: 0.564

Asia WGS AF: 0.575 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.31
PhyloP100		0.013
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: rs908858; hg19: chr1-221883225;