3-52056341-G-A

Variant names:

• chr3-52056341-G-A
• rs1269211669
• NM_001947.4:c.26C>T

Variant summary

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

The NM_001947.4(DUSP7):​c.26C>T​(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000995 in 1,004,528 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. P9A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: DUSP7 NM_001947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 0 publications found

Genes affected

DUSP7 (HGNC:3073): (dual specificity phosphatase 7) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. DUSP7 belongs to a class of DUSPs, designated MKPs, that dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK (see MIM 601795), JNK (see MIM 601158), and p38 (see MIM 600289) with specificity distinct from that of individual MKP proteins. MKPs contain a highly conserved C-terminal catalytic domain and an N-terminal Cdc25 (see MIM 116947)-like (CH2) domain. MAPK activation cascades mediate various physiologic processes, including cellular proliferation, apoptosis, differentiation, and stress responses (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

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=0.11722952).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001947.4. 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
	DUSP7	NM_001947.4	MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 3	NP_001938.2	Q16829-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP7	ENST00000495880.2	TSL:1 MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 3	ENSP00000417183.1	Q16829-1
	DUSP7	ENST00000469623.1	TSL:2	c.-176C>T		upstream_gene	N/A	ENSP00000418566.1	H7C4Z0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.95e-7 AC: 1 AN: 1004528 Hom.: 0 Cov.: 31 AF XY: 0.00000211 AC XY: 1 AN XY: 474218

African (AFR) AF: 0.00 AC: 0 AN: 20068

American (AMR) AF: 0.00 AC: 0 AN: 5804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10746

East Asian (EAS) AF: 0.00 AC: 0 AN: 17958

South Asian (SAS) AF: 0.00 AC: 0 AN: 19482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2484

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 873012

Other (OTH) AF: 0.00 AC: 0 AN: 38022

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.33
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.12	B
Vest4		0.11
MutPred		0.27		Loss of loop (P = 0.0073)
MVP		0.10
MPC		1.6
ClinPred		0.25	T
GERP RS		2.1
PromoterAI		0.0041	Neutral
Varity_R		0.10
gMVP		0.32
Mutation Taster		=95/5	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: rs1269211669; hg19: chr3-52090357;