rs12041033

chr1-221721548-C-Gchr1-221721548-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.812-15082G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 152,268 control chromosomes in the GnomAD database, including 51 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 0.012 (51 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP10	NM_007207.6	c.812-15082G>C		intron_variant		ENST00000366899.4
DUSP10	NR_111939.2	n.59-15082G>C		intron_variant, non_coding_transcript_variant
DUSP10	NR_111940.2	n.110-15082G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP10	ENST00000366899.4	c.812-15082G>C		intron_variant		1	NM_007207.6	P1
DUSP10	ENST00000468085.5	c.-27-15082G>C		intron_variant, NMD_transcript_variant		1
DUSP10	ENST00000477026.5	c.-27-15082G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1764 AN: 152150 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0117 AC: 1775 AN: 152268 Hom.: 51 Cov.: 32 AF XY: 0.0128 AC XY: 951 AN XY: 74450

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.0617

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.000483 Hom.: 0

Bravo AF: 0.0182

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
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: rs12041033; hg19: chr1-221894890;