chr10-75094723-G-C

Position:

• chr10-75094723-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001363514.2(DUSP13B):​c.958C>G​(p.Leu320Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUSP13B NM_001363514.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP13B	NM_001363514.2	c.958C>G	p.Leu320Val	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.958C>G	p.Leu320Val	missense_variant	4/4	5	NM_001363514.2	ENSP00000475626.1
DUSP13	ENST00000473072.3	c.1207C>G	p.Leu403Val	missense_variant	7/7	5		ENSP00000475732.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 10, 2022

The c.829C>G (p.L277V) alteration is located in exon 6 (coding exon 5) of the DUSP13 gene. This alteration results from a C to G substitution at nucleotide position 829, causing the leucine (L) at amino acid position 277 to be replaced by a valine (V). 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	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;D;D;.;D;D;.
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	.;.;D;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	4.1	H;H;.;.;.;H;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;N;D;.;.;.;D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;T;D;.;.;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;D;D
Vest4		0.94
MVP		0.79
MPC		0.63
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.85
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1847655684; hg19: chr10-76854481;