rs4793026

Positions:

• chr17-43773140-A-G
• chr17-43773140-A-T

Variant summary

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

The NM_004090.4(DUSP3):​c.352+1572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,118 control chromosomes in the GnomAD database, including 5,153 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 (5153 hom., cov: 31)
• Consequence: DUSP3 NM_004090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP3	NM_004090.4	c.352+1572T>C		intron_variant		ENST00000226004.8	NP_004081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP3	ENST00000226004.8	c.352+1572T>C		intron_variant		1	NM_004090.4	ENSP00000226004	P1
DUSP3	ENST00000590342.1	c.*499+1572T>C		intron_variant, NMD_transcript_variant		1		ENSP00000467424
DUSP3	ENST00000590753.1	c.132+895T>C		intron_variant		5		ENSP00000466069
DUSP3	ENST00000590935.1	c.363+834T>C		intron_variant		5		ENSP00000468604

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37221 AN: 152000 Hom.: 5128 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.245 AC: 37288 AN: 152118 Hom.: 5153 Cov.: 31 AF XY: 0.243 AC XY: 18049 AN XY: 74358

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.240

Alfa AF: 0.228 Hom.: 836

Bravo AF: 0.247

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.35

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: rs4793026; hg19: chr17-41850508;