5-172769708-G-C

Position:

• chr5-172769708-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004417.4(DUSP1):​c.600C>G​(p.Ile200Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DUSP1 NM_004417.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

Genes affected

DUSP1 (HGNC:3064): (dual specificity phosphatase 1) The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]

ENSG00000253736 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP1	NM_004417.4	c.600C>G	p.Ile200Met	missense_variant	3/4	ENST00000239223.4	NP_004408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP1	ENST00000239223.4	c.600C>G	p.Ile200Met	missense_variant	3/4	1	NM_004417.4	ENSP00000239223.3
ENSG00000253736	ENST00000523005.1	n.69+6660G>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.1	H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.81		Gain of sheet (P = 0.0827);
MVP		0.97
MPC		1.8
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.94
gMVP		0.87

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: rs2431663; hg19: chr5-172196711;