1-159781266-C-G

Position:

• chr1-159781266-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001319658.2(DUSP23):​c.166C>G​(p.Leu56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.387

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09489566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.166C>G	p.Leu56Val	missense_variant	1/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.166C>G	p.Leu56Val	missense_variant	2/3		NP_001306588.1
DUSP23	NM_017823.5	c.166C>G	p.Leu56Val	missense_variant	2/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.166C>G	p.Leu56Val	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.166C>G	p.Leu56Val	missense_variant	2/3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.166C>G	p.Leu56Val	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

Jul 06, 2021

The c.166C>G (p.L56V) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a C to G substitution at nucleotide position 166, causing the leucine (L) at amino acid position 56 to be replaced by a valine (V). 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	Benign	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.54
DEOGEN2	Benign	0.037	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.74	.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.64	N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.72	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.84	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.20
MutPred		0.44		Loss of stability (P = 0.1481);Loss of stability (P = 0.1481);Loss of stability (P = 0.1481);
MVP		0.42
MPC		0.35
ClinPred		0.15	T
GERP RS		4.9
Varity_R		0.31
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-159751056; COSMIC: COSV63660823;