chr10-110498209-C-T

Variant names:

• chr10-110498209-C-T
• rs1859983225
• NM_004419.4:c.88C>T

Variant summary

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

The NM_004419.4(DUSP5):​c.88C>T​(p.Pro30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,361,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: DUSP5 NM_004419.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49
• Publications: 0 publications found

Genes affected

DUSP5 (HGNC:3071): (dual specificity phosphatase 5) 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 product inactivates ERK1, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004419.4. 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
	DUSP5	NM_004419.4	MANE Select	c.88C>T	p.Pro30Ser	missense	Exon 1 of 4	NP_004410.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP5	ENST00000369583.4	TSL:1 MANE Select	c.88C>T	p.Pro30Ser	missense	Exon 1 of 4	ENSP00000358596.3	Q16690
	DUSP5	ENST00000925260.1		c.88C>T	p.Pro30Ser	missense	Exon 1 of 4	ENSP00000595319.1
	DUSP5	ENST00000895745.1		c.88C>T	p.Pro30Ser	missense	Exon 1 of 2	ENSP00000565804.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1361074 Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2 AN XY: 678066

African (AFR) AF: 0.0000358 AC: 1 AN: 27910

American (AMR) AF: 0.00 AC: 0 AN: 37460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22882

East Asian (EAS) AF: 0.00 AC: 0 AN: 30288

South Asian (SAS) AF: 0.00 AC: 0 AN: 80704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062554

Other (OTH) AF: 0.0000182 AC: 1 AN: 55012

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.25
Sift	Benign	0.61	T
Sift4G	Benign	0.71	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.67		Gain of MoRF binding (P = 0.0471)
MVP		0.80
MPC		1.7
ClinPred		0.99	D
GERP RS		4.9
PromoterAI		-0.048	Neutral
Varity_R		0.43
gMVP		0.66
Mutation Taster		=45/55	disease causing

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: rs1859983225; hg19: chr10-112257967;