rs704076

Positions:

• chr12-89350144-C-A
• chr12-89350144-C-T

Variant summary

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

The ENST00000279488.8(DUSP6):​c.838+444G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,162 control chromosomes in the GnomAD database, including 5,186 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 0.24 (5186 hom., cov: 33)
• Consequence: DUSP6 ENST00000279488.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

DUSP6 (HGNC:3072): (dual specificity phosphatase 6) The protein encoded by this gene 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. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Mutations in this gene have been associated with congenital hypogonadotropic hypogonadism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP6	NM_001946.4	c.838+444G>T		intron_variant		ENST00000279488.8	NP_001937.2
DUSP6	NM_022652.4	c.401-583G>T		intron_variant			NP_073143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP6	ENST00000279488.8	c.838+444G>T		intron_variant		1	NM_001946.4	ENSP00000279488	P1
DUSP6	ENST00000308385.6	c.401-583G>T		intron_variant		1		ENSP00000307835
DUSP6	ENST00000547291.1	c.463+444G>T		intron_variant		2		ENSP00000449838
DUSP6	ENST00000547140.1	n.524+444G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36854 AN: 152044 Hom.: 5177 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.243 AC: 36904 AN: 152162 Hom.: 5186 Cov.: 33 AF XY: 0.238 AC XY: 17669 AN XY: 74394

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.224

Alfa AF: 0.143 Hom.: 328

Bravo AF: 0.255

Asia WGS AF: 0.123 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.6
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs704076; hg19: chr12-89743921;