1-159781277-C-G

Position:

• chr1-159781277-C-G

Variant summary

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

The NM_001319658.2(DUSP23):​c.177C>G​(p.His59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H59L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.177C>G	p.His59Gln	missense_variant	1/2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.177C>G	p.His59Gln	missense_variant	2/3		NP_001306588.1
DUSP23	NM_017823.5	c.177C>G	p.His59Gln	missense_variant	2/3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.177C>G	p.His59Gln	missense_variant	1/2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.177C>G	p.His59Gln	missense_variant	2/3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.177C>G	p.His59Gln	missense_variant	2/3	2		ENSP00000357089.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1395614 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 688232

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: 0.00000278

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

Mar 15, 2024

The c.177C>G (p.H59Q) 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 177, causing the histidine (H) at amino acid position 59 to be replaced by a glutamine (Q). 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	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Benign	0.80
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	.;.;T
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.60
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.67
MutPred		0.44		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.99
MPC		1.0
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.59
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr1-159751067;