10-75058417-T-C

Position:

• chr10-75058417-T-C

Variant summary

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

The NM_001003892.3(DUSP29):​c.98A>G​(p.Tyr33Cys) variant causes a missense change. 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: DUSP29 NM_001003892.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.02

Genes affected

DUSP29 (HGNC:23481): (dual specificity phosphatase 29) Enables protein homodimerization activity and protein tyrosine/serine/threonine phosphatase activity. Involved in protein dephosphorylation. Part of protein-containing complex. [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, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP29	NM_001003892.3	c.98A>G	p.Tyr33Cys	missense_variant	2/4	ENST00000338487.6	NP_001003892.1
DUSP29	NM_001384909.1	c.98A>G	p.Tyr33Cys	missense_variant	3/5		NP_001371838.1
DUSP29	XM_017016176.2	c.98A>G	p.Tyr33Cys	missense_variant	2/3		XP_016871665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP29	ENST00000338487.6	c.98A>G	p.Tyr33Cys	missense_variant	2/4	1	NM_001003892.3	ENSP00000340609	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 14, 2024

The c.98A>G (p.Y33C) alteration is located in exon 1 (coding exon 1) of the DUPD1 gene. This alteration results from a A to G substitution at nucleotide position 98, causing the tyrosine (Y) at amino acid position 33 to be replaced by a cysteine (C). 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	0.40
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.42		Loss of sheet (P = 1e-04);
MVP		0.38
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.86
gMVP		0.78

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: chr10-76818175;