chr1-221724965-C-T

Position:

• chr1-221724965-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.811+13969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 152,276 control chromosomes in the GnomAD database, including 50 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 (50 hom., cov: 32)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

DUSP10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP10	NM_007207.6	c.811+13969G>A		intron_variant		ENST00000366899.4	NP_009138.1
DUSP10	NR_111939.2	n.58+11878G>A		intron_variant
DUSP10	NR_111940.2	n.109+17016G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP10	ENST00000366899.4	c.811+13969G>A		intron_variant		1	NM_007207.6	ENSP00000355866.3
DUSP10	ENST00000468085.5	n.-28+11878G>A		intron_variant		1		ENSP00000483812.1
DUSP10	ENST00000477026.5	n.-28+17016G>A		intron_variant		2		ENSP00000482935.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1801 AN: 152158 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0119 AC: 1813 AN: 152276 Hom.: 50 Cov.: 32 AF XY: 0.0130 AC XY: 970 AN XY: 74460

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0163 Hom.: 22

Bravo AF: 0.0185

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.37
DANN	Benign	0.81

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: rs12044821; hg19: chr1-221898307;