Variant 12-89349446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001946.4(DUSP6):c.954T>C(p.Asp318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,148 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 38 hom. )

Consequence

DUSP6
NM_001946.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.611

Variant links:

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]

DUSP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 12-89349446-A-G is Benign according to our data. Variant chr12-89349446-A-G is described in ClinVar as [Benign]. Clinvar id is 783132.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.611 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1683/152304) while in subpopulation AFR AF= 0.0385 (1601/41550). AF 95% confidence interval is 0.037. There are 38 homozygotes in gnomad4. There are 768 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1683 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP6	NM_001946.4 linkuse as main transcript	c.954T>C	p.Asp318=	synonymous_variant	3/3	ENST00000279488.8
DUSP6	NM_022652.4 linkuse as main transcript	c.516T>C	p.Asp172=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP6	ENST00000279488.8 linkuse as main transcript	c.954T>C	p.Asp318=	synonymous_variant	3/3	1	NM_001946.4	P1	Q16828-1
DUSP6	ENST00000308385.6 linkuse as main transcript	c.516T>C	p.Asp172=	synonymous_variant	2/2	1			Q16828-2
DUSP6	ENST00000547291.1 linkuse as main transcript	c.579T>C	p.Asp193=	synonymous_variant	2/2	2
DUSP6	ENST00000547140.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1679

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00718

GnomAD4 exome

AF:

0.00109

AC:

1597

AN:

1461844

Hom.:

Cov.:

AF XY:

0.000939

AC XY:

683

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.0111

AC:

1683

AN:

152304

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00432

Hom.:

Bravo

AF:

0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over