12-12504579-A-G

Position:

• chr12-12504579-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030640.3(DUSP16):​c.368-3897T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,756 control chromosomes in the GnomAD database, including 4,557 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4557 hom., cov: 30)
• Consequence: DUSP16 NM_030640.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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]

DUSP16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP16	NM_030640.3	c.368-3897T>C		intron_variant		ENST00000298573.9	NP_085143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP16	ENST00000298573.9	c.368-3897T>C		intron_variant		1	NM_030640.3	ENSP00000298573.5
DUSP16	ENST00000228862.3	c.367+15283T>C		intron_variant		5		ENSP00000228862.3
DUSP16	ENST00000545864.1	n.100+1509T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33156 AN: 151640 Hom.: 4561 Cov.: 30

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33150 AN: 151756 Hom.: 4557 Cov.: 30 AF XY: 0.225 AC XY: 16685 AN XY: 74130

Gnomad4 AFR AF: 0.0733

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.225

Alfa AF: 0.251 Hom.: 2316

Bravo AF: 0.205

Asia WGS AF: 0.132 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11612508; hg19: chr12-12657513;