5-172770748-C-G

Variant names:

• chr5-172770748-C-G
• rs565966028
• NM_004417.4:c.205G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004417.4(DUSP1):​c.205G>C​(p.Ala69Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000155 in 1,291,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A69T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DUSP1 NM_004417.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20848745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004417.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	NM_004417.4	MANE Select	c.205G>C	p.Ala69Pro	missense	Exon 1 of 4	NP_004408.1	P28562

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	ENST00000239223.4	TSL:1 MANE Select	c.205G>C	p.Ala69Pro	missense	Exon 1 of 4	ENSP00000239223.3	P28562
	DUSP1	ENST00000868089.1		c.205G>C	p.Ala69Pro	missense	Exon 1 of 5	ENSP00000538148.1
	DUSP1	ENST00000868090.1		c.205G>C	p.Ala69Pro	missense	Exon 1 of 5	ENSP00000538149.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1291062 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 632954

African (AFR) AF: 0.00 AC: 0 AN: 25562

American (AMR) AF: 0.00 AC: 0 AN: 21416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21946

East Asian (EAS) AF: 0.00 AC: 0 AN: 28194

South Asian (SAS) AF: 0.0000285 AC: 2 AN: 70202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033206

Other (OTH) AF: 0.00 AC: 0 AN: 53392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		3.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.063
Sift	Benign	0.087	T
Sift4G	Benign	0.23	T
Polyphen		0.18	B
Vest4		0.14
MutPred		0.61		Gain of catalytic residue at A69 (P = 0.0718)
MVP		0.73
MPC		0.91
ClinPred		0.54	D
GERP RS		3.0
PromoterAI		0.073	Neutral
Varity_R		0.40
gMVP		0.58
Mutation Taster		=58/42	polymorphism

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: rs565966028; hg19: chr5-172197751;