17-43768456-G-A

Variant names:

• chr17-43768456-G-A
• rs11713
• ENST00000590342.1:n.*1858C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000590342.1(DUSP3):​n.*1858C>T variant causes a non coding transcript exon 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 ENST00000590342.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590342.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP3	NM_004090.4	MANE Select	c.*1153C>T		3_prime_UTR	Exon 3 of 3	NP_004081.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP3	ENST00000590342.1	TSL:1	n.*1858C>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000467424.1
	DUSP3	ENST00000226004.8	TSL:1 MANE Select	c.*1153C>T		3_prime_UTR	Exon 3 of 3	ENSP00000226004.2
	DUSP3	ENST00000590342.1	TSL:1	n.*1858C>T		3_prime_UTR	Exon 4 of 4	ENSP00000467424.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.429 AC: 6 AN: 14

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.375 AC: 15536 AN: 41398

American (AMR) AF: 0.170 AC: 2601 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5188

South Asian (SAS) AF: 0.176 AC: 843 AN: 4796

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10560

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14374 AN: 67970

Other (OTH) AF: 0.239 AC: 504 AN: 2108

Alfa AF: 0.222 Hom.: 3344

Bravo AF: 0.249

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.61
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11713; hg19: chr17-41845824;