Variant chr1-58782512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002228.4(JUN):c.559G>T(p.Ala187Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,418,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

JUN
NM_002228.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

Variant links:

Genes affected

JUN (HGNC:6204): (Jun proto-oncogene, AP-1 transcription factor subunit) This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. [provided by RefSeq, Jul 2008]

JUN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1879077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUN	NM_002228.4 linkuse as main transcript	c.559G>T	p.Ala187Ser	missense_variant	1/1	ENST00000371222.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
JUN	ENST00000371222.4 linkuse as main transcript	c.559G>T	p.Ala187Ser	missense_variant	1/1	NM_002228.4	P1
JUN	ENST00000710273.1 linkuse as main transcript	c.625G>T	p.Ala209Ser	missense_variant	1/1
JUN	ENST00000678696.1 linkuse as main transcript	c.559G>T	p.Ala187Ser	missense_variant, NMD_transcript_variant	1/4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177482

Hom.:

AF XY:

0.0000202

AC XY:

AN XY:

98922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000263

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1418744

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

703678

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 31, 2023

The c.559G>T (p.A187S) alteration is located in exon 1 (coding exon 1) of the JUN gene. This alteration results from a G to T substitution at nucleotide position 559, causing the alanine (A) at amino acid position 187 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

0.075

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.073

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.0015

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.40

M_CAP

Benign

0.028

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.55

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.74

REVEL

Benign

0.073

Sift

Benign

0.14

Sift4G

Benign

0.34

Polyphen

0.095

Vest4

0.31

MutPred

0.48

Gain of glycosylation at A187 (P = 0.0049);

MVP

0.37

MPC

0.91

ClinPred

0.26

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.13

gMVP

0.22

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