10-75043923-C-G

Variant names:

• chr10-75043923-C-G
• NM_001003892.3:c.295G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003892.3(DUSP29):​c.295G>C​(p.Asp99His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D99N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DUSP29 NM_001003892.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53

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]

ENSG00000285810 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10549179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP29	NM_001003892.3	c.295G>C	p.Asp99His	missense_variant	Exon 3 of 4	ENST00000338487.6	NP_001003892.1
DUSP29	NM_001384909.1	c.295G>C	p.Asp99His	missense_variant	Exon 4 of 5		NP_001371838.1
DUSP29	XM_017016176.2	c.*761G>C		downstream_gene_variant			XP_016871665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP29	ENST00000338487.6	c.295G>C	p.Asp99His	missense_variant	Exon 3 of 4	1	NM_001003892.3	ENSP00000340609.5
ENSG00000285810	ENST00000649504.1	n.91+1957C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461542 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.073
Sift	Benign	0.075	T
Sift4G	Benign	0.077	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.47		Loss of sheet (P = 0.0817);
MVP		0.32
MPC		0.44
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.41
gMVP		0.66

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: chr10-76803681;