1-159781134-C-A

Position:

• chr1-159781134-C-A

Variant summary

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

The NM_001319658.2(DUSP23):​c.34C>A​(p.Leu12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43

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=0.10696828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.34C>A	p.Leu12Ile	missense_variant	1/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.34C>A	p.Leu12Ile	missense_variant	2/3		NP_001306588.1
DUSP23	NM_017823.5	c.34C>A	p.Leu12Ile	missense_variant	2/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.34C>A	p.Leu12Ile	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.34C>A	p.Leu12Ile	missense_variant	2/3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.34C>A	p.Leu12Ile	missense_variant	2/3	2		ENSP00000357089.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 688786

Gnomad4 AFR exome AF: 0.0000317

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000148 AC: 1

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

Dec 14, 2023

The c.34C>A (p.L12I) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a C to A substitution at nucleotide position 34, causing the leucine (L) at amino acid position 12 to be replaced by an isoleucine (I). 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	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0072	T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.77	N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.61	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.44		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.42
MPC		0.37
ClinPred		0.70	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.32
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs757046968; hg19: chr1-159750924;