1-159781299-T-C

Position:

• chr1-159781299-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001319658.2(DUSP23):​c.199T>C​(p.Cys67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000574 in 1,394,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C67F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30081838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.199T>C	p.Cys67Arg	missense_variant	1/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.199T>C	p.Cys67Arg	missense_variant	2/3		NP_001306588.1
DUSP23	NM_017823.5	c.199T>C	p.Cys67Arg	missense_variant	2/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.199T>C	p.Cys67Arg	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.199T>C	p.Cys67Arg	missense_variant	2/3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.199T>C	p.Cys67Arg	missense_variant	2/3	2		ENSP00000357089.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000574 AC: 8 AN: 1394496 Hom.: 0 Cov.: 32 AF XY: 0.00000582 AC XY: 4 AN XY: 687574

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: 0.00

Gnomad4 NFE exome AF: 0.00000742

Gnomad4 OTH exome AF: 0.00

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

Jan 17, 2023

The c.199T>C (p.C67R) alteration is located in exon 2 (coding exon 1) of the DUSP23 gene. This alteration results from a T to C substitution at nucleotide position 199, causing the cysteine (C) at amino acid position 67 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.85
DEOGEN2	Benign	0.057	T;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	.;.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.28	N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.70	P;P;P
Vest4		0.24
MutPred		0.43		Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);
MVP		0.85
MPC		0.61
ClinPred		0.53	D
GERP RS		4.8
Varity_R		0.78
gMVP		0.83

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: rs1661861346; hg19: chr1-159751089;