12-12477747-TGGGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030640.3(DUSP16):c.1080_1083del(p.Pro361AlafsTer10) variant causes a frameshift change. The variant allele was found at a frequency of 0.0235 in 1,613,570 control chromosomes in the GnomAD database, including 2,919 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. V360V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.026 (281 hom., cov: 32)
  • Exomes 𝑓: 0.023 (2638 hom.)
• Consequence: DUSP16 NM_030640.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.84

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 -10 ACMG points.

• BP6: Variant 12-12477747-TGGGC-T is Benign according to our data. Variant chr12-12477747-TGGGC-T is described in ClinVar as [Benign]. Clinvar id is 771457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP16	NM_030640.3	c.1080_1083del	p.Pro361AlafsTer10	frameshift_variant	7/7	ENST00000298573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP16	ENST00000298573.9	c.1080_1083del	p.Pro361AlafsTer10	frameshift_variant	7/7	1	NM_030640.3	P1
DUSP16	ENST00000228862.3	c.*484_*487del		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3901 AN: 152194 Hom.: 279 Cov.: 32

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00398

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0456 AC: 11302 AN: 247784 Hom.: 1105 AF XY: 0.0446 AC XY: 5984 AN XY: 134188

Gnomad AFR exome AF: 0.00255

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.00956

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.00411

Gnomad OTH exome AF: 0.0290

GnomAD4 exome AF: 0.0232 AC: 33954 AN: 1461258 Hom.: 2638 AF XY: 0.0255 AC XY: 18548 AN XY: 726872

Gnomad4 AFR exome AF: 0.00263

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0268

Gnomad4 NFE exome AF: 0.00336

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.0257 AC: 3911 AN: 152312 Hom.: 281 Cov.: 32 AF XY: 0.0306 AC XY: 2278 AN XY: 74474

Gnomad4 AFR AF: 0.00452

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.00398

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0103 Hom.: 4

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs200271649; hg19: chr12-12630681;