Variant 11-65900309-T-C 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_005438.5(FOSL1):c.31A>G(p.Ser11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,091,714 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: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

FOSL1
NM_005438.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.253

Variant links:

Genes affected

FOSL1 (HGNC:13718): (FOS like 1, AP-1 transcription factor subunit) The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

FOSL1 links:

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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=0.14858934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOSL1	NM_005438.5 linkuse as main transcript	c.31A>G	p.Ser11Gly	missense_variant	1/4	ENST00000312562.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOSL1	ENST00000312562.7 linkuse as main transcript	c.31A>G	p.Ser11Gly	missense_variant	1/4	1	NM_005438.5	P1	P15407-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1091714

Hom.:

Cov.:

AF XY:

0.00000386

AC XY:

AN XY:

518304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000227

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 30, 2024

The c.31A>G (p.S11G) alteration is located in exon 1 (coding exon 1) of the FOSL1 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the serine (S) at amino acid position 11 to be replaced by a glycine (G). 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

0.084

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

.;T;.;T

Eigen

Benign

-0.068

Eigen_PC

Benign

0.017

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.46

T;T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

0.56

D;D;D;D;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.11

T;D;D;D

Sift4G

Pathogenic

0.0

D;T;T;D

Polyphen

0.78

.;P;.;.

Vest4

0.23

MutPred

0.14

Loss of phosphorylation at S11 (P = 0.0147);Loss of phosphorylation at S11 (P = 0.0147);Loss of phosphorylation at S11 (P = 0.0147);Loss of phosphorylation at S11 (P = 0.0147);

MVP

0.72

MPC

0.42

ClinPred

0.72

GERP RS

4.4

Varity_R

0.13

gMVP

0.29

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