17-43768035-C-T

Position:

• chr17-43768035-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.*1574G>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 0.663 in 152,082 control chromosomes in the GnomAD database, including 34,389 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 0.66 (34387 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: DUSP3 NM_004090.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP3	NM_004090.4	c.*1574G>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	ENST00000226004.8	c.*1574G>A		3_prime_UTR_variant	3/3	1	NM_004090.4	ENSP00000226004	P1
DUSP3	ENST00000590935.1	c.*1746G>A		3_prime_UTR_variant	3/3	5		ENSP00000468604
DUSP3	ENST00000590753.1	c.*28-1251G>A		intron_variant		5		ENSP00000466069

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100805 AN: 151960 Hom.: 34382 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.663 AC: 100833 AN: 152078 Hom.: 34387 Cov.: 32 AF XY: 0.668 AC XY: 49667 AN XY: 74340

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.662

Alfa AF: 0.686 Hom.: 12036

Bravo AF: 0.653

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.64

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: rs1230399; hg19: chr17-41845403;