12-12477673-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_030640.3(DUSP16):c.1158C>T(p.Ser386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,614,028 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (73 hom.)
• Consequence: DUSP16 NM_030640.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.643

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-12477673-G-A is Benign according to our data. Variant chr12-12477673-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.643 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP16	NM_030640.3	c.1158C>T	p.Ser386=	synonymous_variant	7/7	ENST00000298573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP16	ENST00000298573.9	c.1158C>T	p.Ser386=	synonymous_variant	7/7	1	NM_030640.3	P1
DUSP16	ENST00000228862.3	c.*562C>T		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 1010 AN: 152250 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00867

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00731 AC: 1836 AN: 251262 Hom.: 15 AF XY: 0.00719 AC XY: 976 AN XY: 135806

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00668

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00743

Gnomad NFE exome AF: 0.00870

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.00882 AC: 12897 AN: 1461660 Hom.: 73 Cov.: 31 AF XY: 0.00861 AC XY: 6264 AN XY: 727124

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00657

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.00701

Gnomad4 NFE exome AF: 0.00947

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.00663 AC: 1010 AN: 152368 Hom.: 6 Cov.: 32 AF XY: 0.00652 AC XY: 486 AN XY: 74510

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00751

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.00867

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00962 Hom.: 7

Bravo AF: 0.00645

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00916

EpiControl AF: 0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DUSP16: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.1
Dann	Benign	0.55

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: rs112390593; hg19: chr12-12630607; COSMIC: COSV53807916; COSMIC: COSV53807916;