Variant 19-18280458-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005354.6(JUND):c.1027C>G(p.Gln343Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,410,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

JUND
NM_005354.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17725968).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JUND	NM_005354.6 linkuse as main transcript	c.1027C>G	p.Gln343Glu	missense_variant	1/1	ENST00000252818.5	NP_005345.3
JUND	NM_001286968.2 linkuse as main transcript	c.898C>G	p.Gln300Glu	missense_variant	1/1		NP_001273897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JUND	ENST00000252818.5 linkuse as main transcript	c.1027C>G	p.Gln343Glu	missense_variant	1/1		NM_005354.6	ENSP00000252818	P1
JUND	ENST00000600972.1 linkuse as main transcript	c.472C>G	p.Gln158Glu	missense_variant, splice_region_variant	1/2	2		ENSP00000475153

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000600

AC:

AN:

166752

Hom.:

AF XY:

0.0000110

AC XY:

AN XY:

90574

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:

0.0000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1410252

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000552

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 17, 2022

The c.1027C>G (p.Q343E) alteration is located in exon 1 (coding exon 1) of the JUND gene. This alteration results from a C to G substitution at nucleotide position 1027, causing the glutamine (Q) at amino acid position 343 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.61

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.038

Sift

Benign

0.054

T;.

Sift4G

Benign

0.061

T;.

Polyphen

0.053

B;.

Vest4

0.13

MutPred

0.17

Gain of phosphorylation at Y347 (P = 0.1218);.;

MVP

0.39

ClinPred

0.73

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.30

gMVP

0.52

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