chr10-75094749-C-A

Position:

• chr10-75094749-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363514.2(DUSP13B):​c.932G>T​(p.Cys311Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.05

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP13B	NM_001363514.2	c.932G>T	p.Cys311Phe	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.932G>T	p.Cys311Phe	missense_variant	4/4	5	NM_001363514.2	ENSP00000475626.1
DUSP13	ENST00000473072.3	c.1181G>T	p.Cys394Phe	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

Feb 21, 2024

The c.803G>T (p.C268F) alteration is located in exon 6 (coding exon 5) of the DUSP13 gene. This alteration results from a G to T substitution at nucleotide position 803, causing the cysteine (C) at amino acid position 268 to be replaced by a phenylalanine (F). 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	0.28
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.49	T;T;D;.;T;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	.;.;D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.42	N;N;.;.;.;N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.0	D;.;D;.;.;.;D
REVEL	Benign	0.20
Sift	Benign	0.72	T;.;T;.;.;.;T
Sift4G	Benign	0.83	T;T;T;T;T;T;T
Polyphen		0.33	B;B;.;.;.;B;P
Vest4		0.67
MVP		0.51
MPC		0.38
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-76854507;