17-43769100-C-T

Position:

• chr17-43769100-C-T

Variant summary

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

The NM_004090.4(DUSP3):​c.*509G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 153,440 control chromosomes in the GnomAD database, including 2,244 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 0.15 (2217 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27 hom.)
• Consequence: DUSP3 NM_004090.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP3	NM_004090.4	c.*509G>A		3_prime_UTR_variant	3/3	ENST00000226004.8	NP_004081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP3	ENST00000226004	c.*509G>A		3_prime_UTR_variant	3/3	1	NM_004090.4	ENSP00000226004.2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23082 AN: 152132 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.195 AC: 232 AN: 1190 Hom.: 27 Cov.: 0 AF XY: 0.191 AC XY: 130 AN XY: 680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.152 AC: 23084 AN: 152250 Hom.: 2217 Cov.: 32 AF XY: 0.152 AC XY: 11305 AN XY: 74442

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.170

Alfa AF: 0.173 Hom.: 890

Bravo AF: 0.141

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.52

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: rs17742347; hg19: chr17-41846468; COSMIC: COSV56825886;