1-159781339-T-G

Position:

• chr1-159781339-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001319658.2(DUSP23):​c.239T>G​(p.Ile80Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

Genes affected

DUSP23 (HGNC:21480): (dual specificity phosphatase 23) Enables protein tyrosine/serine/threonine phosphatase activity. Involved in dephosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.239T>G	p.Ile80Ser	missense_variant	1/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.239T>G	p.Ile80Ser	missense_variant	2/3		NP_001306588.1
DUSP23	NM_017823.5	c.239T>G	p.Ile80Ser	missense_variant	2/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.239T>G	p.Ile80Ser	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.239T>G	p.Ile80Ser	missense_variant	2/3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.239T>G	p.Ile80Ser	missense_variant	2/3	2		ENSP00000357089.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.239T>G (p.I80S) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a T to G substitution at nucleotide position 239, causing the isoleucine (I) at amino acid position 80 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;T;T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.0078
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	.;.;T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.93	P;P;P
Vest4		0.71
MutPred		0.63		Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);
MVP		0.97
MPC		1.3
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.87
gMVP		0.91

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159751129;