10-75094806-C-T

Position:

• chr10-75094806-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001363514.2(DUSP13B):​c.875G>A​(p.Cys292Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,613,762 control chromosomes in the GnomAD database, including 179,702 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22654 hom., cov: 33)
  • Exomes 𝑓: 0.45 (157048 hom.)
• Consequence: DUSP13B NM_001363514.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236

Genes affected

DUSP13B (HGNC:19681): (dual specificity phosphatase 13B) Members of the protein-tyrosine phosphatase superfamily cooperate with protein kinases to regulate cell proliferation and differentiation. This gene encodes a dual specificity phosphatase that acts on both phosphotyrosine and phosphoserine/threonine residues. The encoded protein is expressed in testis. [provided by RefSeq, Mar 2023]

DUSP13 (HGNC:):

DUSP13 (HGNC:56772): (dual specificity phosphatase 13A) Members of the protein-tyrosine phosphatase superfamily cooperate with protein kinases to regulate cell proliferation and differentiation. This gene encodes a dual specificity phosphatase that acts on both phosphotyrosine and phosphoserine/threonine residues. The encoded protein is expressed in skeletal muscle. [provided by RefSeq, Mar 2023]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.441111E-7).
• BP6: Variant 10-75094806-C-T is Benign according to our data. Variant chr10-75094806-C-T is described in ClinVar as [Benign]. Clinvar id is 1179558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP13B	NM_001363514.2	c.875G>A	p.Cys292Tyr	missense_variant	4/4	ENST00000478873.7	NP_001350443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP13	ENST00000478873.7	c.875G>A	p.Cys292Tyr	missense_variant	4/4	5	NM_001363514.2	ENSP00000475626.1
DUSP13	ENST00000473072.3	c.1124G>A	p.Cys375Tyr	missense_variant	7/7	5		ENSP00000475732.2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80499 AN: 151970 Hom.: 22621 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.530

GnomAD3 exomes AF: 0.527 AC: 132191 AN: 250674 Hom.: 38194 AF XY: 0.511 AC XY: 69269 AN XY: 135536

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.742

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.907

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.450 AC: 658482 AN: 1461674 Hom.: 157048 Cov.: 57 AF XY: 0.450 AC XY: 326964 AN XY: 727106

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.530 AC: 80580 AN: 152088 Hom.: 22654 Cov.: 33 AF XY: 0.534 AC XY: 39701 AN XY: 74362

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.534

Alfa AF: 0.449 Hom.: 40957

Bravo AF: 0.555

TwinsUK AF: 0.410 AC: 1519

ALSPAC AF: 0.405 AC: 1559

ESP6500AA AF: 0.659 AC: 2903

ESP6500EA AF: 0.426 AC: 3663

ExAC AF: 0.518 AC: 62862

Asia WGS AF: 0.717 AC: 2493 AN: 3478

EpiCase AF: 0.429

EpiControl AF: 0.427

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 21085059) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.4
DANN	Benign	0.88
DEOGEN2	Benign	0.15	T;T;T;.;T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.32	.;.;T;T;T;T;T
MetaRNN	Benign	5.4e-7	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N;N;.;.;.;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.3	N;.;N;.;.;.;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;.;T;.;.;.;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0050	B;B;.;.;.;B;B
Vest4		0.056
MPC		0.25
ClinPred		0.00026	T
GERP RS		-2.2
Varity_R		0.11
gMVP		0.68

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: rs3088142; hg19: chr10-76854564;