12-12477789-C-T

Variant summary

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

The NM_030640.3(DUSP16):c.1042G>A(p.Glu348Lys) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUSP16 NM_030640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

Genes affected

DUSP16 (HGNC:17909): (dual specificity phosphatase 16) This gene encodes a mitogen-activated protein kinase phosphatase that is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. The encoded protein specifically regulates the c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways.[provided by RefSeq, May 2010]

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=0.15424952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP16	NM_030640.3	c.1042G>A	p.Glu348Lys	missense_variant	7/7	ENST00000298573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP16	ENST00000298573.9	c.1042G>A	p.Glu348Lys	missense_variant	7/7	1	NM_030640.3	P1
DUSP16	ENST00000228862.3	c.*446G>A		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250708 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135630

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Nov 18, 2022

The c.1042G>A (p.E348K) alteration is located in exon 7 (coding exon 6) of the DUSP16 gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the glutamic acid (E) at amino acid position 348 to be replaced by a lysine (K). 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	0.086
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.69	T
Polyphen		0.22	B
Vest4		0.18
MutPred		0.29		Gain of ubiquitination at E348 (P = 0.0029);
MVP		0.63
ClinPred		0.33	T
GERP RS		5.0
Varity_R		0.23
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1425928935; hg19: chr12-12630723;