rs12126069

chr1-221707509-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007207.6(DUSP10):c.812-1043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,028 control chromosomes in the GnomAD database, including 12,223 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 0.38 (12223 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP10	NM_007207.6	c.812-1043T>C		intron_variant		ENST00000366899.4
DUSP10	XM_047442948.1	c.29-1043T>C		intron_variant
DUSP10	NR_111939.2	n.59-1043T>C		intron_variant, non_coding_transcript_variant
DUSP10	NR_111940.2	n.110-1043T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP10	ENST00000366899.4	c.812-1043T>C		intron_variant		1	NM_007207.6	P1
DUSP10	ENST00000468085.5	c.-27-1043T>C		intron_variant, NMD_transcript_variant		1
DUSP10	ENST00000477026.5	c.-27-1043T>C		intron_variant, NMD_transcript_variant		2
DUSP10	ENST00000494642.1	c.-27-1043T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57060 AN: 151910 Hom.: 12221 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.375 AC: 57074 AN: 152028 Hom.: 12223 Cov.: 32 AF XY: 0.377 AC XY: 27997 AN XY: 74302

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.411

Alfa AF: 0.409 Hom.: 2311

Bravo AF: 0.359

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.7
Dann	Benign	0.76

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: rs12126069; hg19: chr1-221880851;