chr17-37512318-C-T

Position:

• chr17-37512318-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007026.4(DUSP14):​c.46C>T​(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DUSP14 NM_007026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

DUSP14 (HGNC:17007): (dual specificity phosphatase 14) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP14 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28979707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP14	NM_007026.4	c.46C>T	p.Pro16Ser	missense_variant	3/3	ENST00000617516.5	NP_008957.1
DUSP14	XM_005256977.4	c.46C>T	p.Pro16Ser	missense_variant	3/3		XP_005257034.1
DUSP14	XM_011524234.2	c.46C>T	p.Pro16Ser	missense_variant	3/3		XP_011522536.1
DUSP14	XM_047435217.1	c.46C>T	p.Pro16Ser	missense_variant	3/3		XP_047291173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP14	ENST00000617516.5	c.46C>T	p.Pro16Ser	missense_variant	3/3	1	NM_007026.4	ENSP00000478595.1
DUSP14	ENST00000613659.1	c.46C>T	p.Pro16Ser	missense_variant	3/3	2		ENSP00000484091.1
DUSP14	ENST00000614411.1	c.46C>T	p.Pro16Ser	missense_variant	2/2	2		ENSP00000477653.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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 03, 2023

The c.46C>T (p.P16S) alteration is located in exon 3 (coding exon 1) of the DUSP14 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the proline (P) at amino acid position 16 to be replaced by a serine (S). 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	0.19
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T;T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.36
MutPred		0.28		Gain of phosphorylation at P16 (P = 0.0463);Gain of phosphorylation at P16 (P = 0.0463);Gain of phosphorylation at P16 (P = 0.0463);
MVP		0.60
ClinPred		0.79	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.72

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: chr17-35872420;