rs11713

chr17-43768456-G-A

Variant summary

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

The NM_004090.4(DUSP3):c.*1153C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,976 control chromosomes in the GnomAD database, including 5,203 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 0.25 (5203 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: DUSP3 NM_004090.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

Genes affected

DUSP3 (HGNC:3069): (dual specificity phosphatase 3) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP3	NM_004090.4	c.*1153C>T		3_prime_UTR_variant	3/3	ENST00000226004.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP3	ENST00000226004.8	c.*1153C>T		3_prime_UTR_variant	3/3	1	NM_004090.4	P1
DUSP3	ENST00000590342.1	c.*1858C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1
DUSP3	ENST00000590935.1	c.*1325C>T		3_prime_UTR_variant	3/3	5
DUSP3	ENST00000590753.1	c.*27+1126C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37314 AN: 151834 Hom.: 5179 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.333 AC: 8 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.438 AC XY: 7 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.246 AC: 37383 AN: 151952 Hom.: 5203 Cov.: 32 AF XY: 0.243 AC XY: 18084 AN XY: 74282

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.239

Alfa AF: 0.223 Hom.: 2272

Bravo AF: 0.249

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.38
Dann	Benign	0.61

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: rs11713; hg19: chr17-41845824;