17-43768035-C-T

Variant names:

• chr17-43768035-C-T
• rs1230399
• NM_004090.4:c.*1574G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.83).
• 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 rank	MANE	Protein	UniProt
DUSP3	NM_004090.4	c.*1574G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000226004.8	NP_004081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP3	ENST00000226004.8	c.*1574G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_004090.4	ENSP00000226004.2
DUSP3	ENST00000590935.1	c.*1746G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000468604.1
DUSP3	ENST00000590753.1	c.*28-1251G>A		intron_variant	Intron 3 of 3	5		ENSP00000466069.1

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

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: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.493 AC: 20445 AN: 41456

American (AMR) AF: 0.755 AC: 11528 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4440 AN: 5174

South Asian (SAS) AF: 0.712 AC: 3437 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8040 AN: 10556

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48612 AN: 68008

Other (OTH) AF: 0.662 AC: 1395 AN: 2108

Alfa AF: 0.687 Hom.: 19852

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
PhyloP100		0.78
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: rs1230399; hg19: chr17-41845403;