rs769352051

Variant names:

• chr10-110498239-C-A
• rs769352051
• NM_004419.4:c.118C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110498239-C-A
• chr10-110498239-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004419.4(DUSP5):​c.118C>A​(p.Arg40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,356,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R40C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: DUSP5 NM_004419.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP5	NM_004419.4	c.118C>A	p.Arg40Ser	missense_variant	Exon 1 of 4	ENST00000369583.4	NP_004410.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP5	ENST00000369583.4	c.118C>A	p.Arg40Ser	missense_variant	Exon 1 of 4	1	NM_004419.4	ENSP00000358596.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000221 AC: 3 AN: 1356904 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000256

Gnomad4 NFE exome AF: 0.00000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000845 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.18
Sift	Benign	0.16	T
Sift4G	Benign	0.35	T
Polyphen		0.98	D
Vest4		0.39
MutPred		0.53		Loss of MoRF binding (P = 0.0152);
MVP		0.62
MPC		1.2
ClinPred		0.65	D
GERP RS		4.9
Varity_R		0.52
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs769352051; hg19: chr10-112257997;