1-221702417-C-T

Variant names:

• chr1-221702417-C-T
• rs934002658
• NM_007207.6:c.1444G>A

Variant summary

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

The NM_007207.6(DUSP10):​c.1444G>A​(p.Val482Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V482L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUSP10 NM_007207.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

Genes affected

DUSP10 (HGNC:3065): (dual specificity phosphatase 10) Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the MAP kinase superfamily, which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity phosphatases show distinct substrate specificities for MAP kinases, different tissue distribution and subcellular localization, and different modes of expression induction by extracellular stimuli. This gene product binds to and inactivates p38 and SAPK/JNK. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

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_007207.6. 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
	DUSP10	NM_007207.6	MANE Select	c.1444G>A	p.Val482Met	missense	Exon 4 of 4	NP_009138.1	Q9Y6W6-1
	DUSP10	NR_111939.2		n.691G>A		non_coding_transcript_exon	Exon 3 of 3
	DUSP10	NR_111940.2		n.742G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP10	ENST00000366899.4	TSL:1 MANE Select	c.1444G>A	p.Val482Met	missense	Exon 4 of 4	ENSP00000355866.3	Q9Y6W6-1
	DUSP10	ENST00000468085.5	TSL:1	n.*405G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000483812.1	A0A0B4J2F5
	DUSP10	ENST00000468085.5	TSL:1	n.*405G>A		3_prime_UTR	Exon 3 of 3	ENSP00000483812.1	A0A0B4J2F5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	M
PhyloP100		7.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.26		Gain of disorder (P = 0.0941)
MVP		0.64
MPC		1.1
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.69
gMVP		0.81
Mutation Taster		=28/72	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: rs934002658; hg19: chr1-221875759;