1-221709883-C-T

Position:

• chr1-221709883-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP10	NM_007207.6	c.812-3417G>A		intron_variant		ENST00000366899.4	NP_009138.1
DUSP10	XM_047442948.1	c.29-3417G>A		intron_variant			XP_047298904.1
DUSP10	NR_111939.2	n.59-3417G>A		intron_variant
DUSP10	NR_111940.2	n.110-3417G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP10	ENST00000366899.4	c.812-3417G>A		intron_variant		1	NM_007207.6	ENSP00000355866.3
DUSP10	ENST00000468085.5	n.-27-3417G>A		intron_variant		1		ENSP00000483812.1
DUSP10	ENST00000477026.5	n.-27-3417G>A		intron_variant		2		ENSP00000482935.1
DUSP10	ENST00000494642.1	n.-28+1754G>A		intron_variant		2		ENSP00000480008.1

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

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.585

Alfa AF: 0.580 Hom.: 19748

Bravo AF: 0.564

Asia WGS AF: 0.575 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.31

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: rs908858; hg19: chr1-221883225;