Variant chr19-18281235-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005354.6(JUND):c.250C>T(p.Pro84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000989 in 1,486,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

JUND
NM_005354.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0950

Variant links:

Genes affected

JUND (HGNC:6206): (JunD proto-oncogene, AP-1 transcription factor subunit) The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. This protein has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternative translation initiation site usage results in the production of different isoforms (PMID:12105216). [provided by RefSeq, Nov 2013]

JUND links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016432673).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUND	NM_005354.6 linkuse as main transcript	c.250C>T	p.Pro84Ser	missense_variant	1/1	ENST00000252818.5
JUND	NM_001286968.2 linkuse as main transcript	c.121C>T	p.Pro41Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JUND	ENST00000252818.5 linkuse as main transcript	c.250C>T	p.Pro84Ser	missense_variant	1/1		NM_005354.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000444

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000367

AC:

AN:

95454

Hom.:

AF XY:

0.000350

AC XY:

AN XY:

54224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.000368

GnomAD4 exome

AF:

0.000105

AC:

140

AN:

1335640

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

659352

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000862

Gnomad4 OTH exome

AF:

0.000181

GnomAD4 genome

AF:

0.0000464

AC:

AN:

150734

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73608

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000444

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000128

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.250C>T (p.P84S) alteration is located in exon 1 (coding exon 1) of the JUND gene. This alteration results from a C to T substitution at nucleotide position 250, causing the proline (P) at amino acid position 84 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.33

REVEL

Benign

0.075

Sift

Benign

0.63

Sift4G

Benign

0.61

Polyphen

0.99

Vest4

0.042

MutPred

0.45

Gain of relative solvent accessibility (P = 0.005);

MVP

0.47

ClinPred

0.14

GERP RS

1.1

Varity_R

0.052

gMVP

0.26

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

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