rs1129923

Variant names:

• chr1-159782276-G-A
• rs1129923
• NM_001319658.2:c.391G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-159782276-G-A
• chr1-159782276-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319658.2(DUSP23):​c.391G>A​(p.Gly131Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,613,962 control chromosomes in the GnomAD database, including 7,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (528 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6597 hom.)
• Consequence: DUSP23 NM_001319658.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.51
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019216537).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP23	NM_001319658.2	c.391G>A	p.Gly131Ser	missense_variant	Exon 2 of 2	ENST00000368107.2	NP_001306587.1
DUSP23	NM_001319659.2	c.391G>A	p.Gly131Ser	missense_variant	Exon 3 of 3		NP_001306588.1
DUSP23	NM_017823.5	c.391G>A	p.Gly131Ser	missense_variant	Exon 3 of 3		NP_060293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP23	ENST00000368107.2	c.391G>A	p.Gly131Ser	missense_variant	Exon 2 of 2	1	NM_001319658.2	ENSP00000357087.1
DUSP23	ENST00000368108.7	c.391G>A	p.Gly131Ser	missense_variant	Exon 3 of 3	1		ENSP00000357088.3
DUSP23	ENST00000368109.5	c.391G>A	p.Gly131Ser	missense_variant	Exon 3 of 3	2		ENSP00000357089.1

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10910 AN: 151958 Hom.: 529 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.0762

GnomAD2 exomes AF: 0.0848 AC: 21319 AN: 251476 AF XY: 0.0892

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0400

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.00446

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.0972

Gnomad OTH exome AF: 0.0924

GnomAD4 exome AF: 0.0910 AC: 133102 AN: 1461884 Hom.: 6597 Cov.: 31 AF XY: 0.0926 AC XY: 67341 AN XY: 727242

African (AFR) AF: 0.0138 AC: 461 AN: 33480

American (AMR) AF: 0.0430 AC: 1925 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3199 AN: 26134

East Asian (EAS) AF: 0.00239 AC: 95 AN: 39700

South Asian (SAS) AF: 0.123 AC: 10616 AN: 86258

European-Finnish (FIN) AF: 0.135 AC: 7186 AN: 53418

Middle Eastern (MID) AF: 0.0501 AC: 289 AN: 5768

European-Non Finnish (NFE) AF: 0.0936 AC: 104099 AN: 1112006

Other (OTH) AF: 0.0866 AC: 5232 AN: 60396

GnomAD4 genome AF: 0.0717 AC: 10904 AN: 152078 Hom.: 528 Cov.: 32 AF XY: 0.0734 AC XY: 5459 AN XY: 74362

African (AFR) AF: 0.0150 AC: 624 AN: 41480

American (AMR) AF: 0.0623 AC: 952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5178

South Asian (SAS) AF: 0.129 AC: 621 AN: 4802

European-Finnish (FIN) AF: 0.135 AC: 1431 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0962 AC: 6540 AN: 67962

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0871 Hom.: 3029

Bravo AF: 0.0619

TwinsUK AF: 0.0949 AC: 352

ALSPAC AF: 0.0848 AC: 327

ESP6500AA AF: 0.0166 AC: 73

ESP6500EA AF: 0.0921 AC: 792

ExAC AF: 0.0850 AC: 10325

Asia WGS AF: 0.0640 AC: 224 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.0972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	.;.;D
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M;M;M
PhyloP100		9.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.47
MPC		1.1
ClinPred		0.020	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.80
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1129923; hg19: chr1-159752066; COSMIC: COSV63660398;