chr1-221724004-A-C

Position:

• chr1-221724004-A-C

Variant summary

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

The NM_007207.6(DUSP10):​c.811+14930T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,120 control chromosomes in the GnomAD database, including 14,836 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 0.41 (14836 hom., cov: 33)
• Consequence: DUSP10 NM_007207.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP10	NM_007207.6	c.811+14930T>G		intron_variant		ENST00000366899.4	NP_009138.1
DUSP10	NR_111939.2	n.58+12839T>G		intron_variant, non_coding_transcript_variant
DUSP10	NR_111940.2	n.110-17538T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP10	ENST00000366899.4	c.811+14930T>G		intron_variant		1	NM_007207.6	ENSP00000355866	P1
DUSP10	ENST00000468085.5	c.-28+12839T>G		intron_variant, NMD_transcript_variant		1		ENSP00000483812
DUSP10	ENST00000477026.5	c.-27-17538T>G		intron_variant, NMD_transcript_variant		2		ENSP00000482935

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62724 AN: 152002 Hom.: 14844 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.412 AC: 62721 AN: 152120 Hom.: 14836 Cov.: 33 AF XY: 0.406 AC XY: 30238 AN XY: 74404

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.460

Alfa AF: 0.374 Hom.: 1707

Bravo AF: 0.396

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.33

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: rs11118838; hg19: chr1-221897346; COSMIC: COSV60457028;