11-65896873-G-T

Position:

• chr11-65896873-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005438.5(FOSL1):​c.233C>A​(p.Pro78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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 (HGNC:):

ACMG classification

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=0.23010543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL1	NM_005438.5	c.233C>A	p.Pro78His	missense_variant	2/4	ENST00000312562.7	NP_005429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOSL1	ENST00000312562.7	c.233C>A	p.Pro78His	missense_variant	2/4	1	NM_005438.5	ENSP00000310170.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 22, 2024

The c.233C>A (p.P78H) alteration is located in exon 2 (coding exon 2) of the FOSL1 gene. This alteration results from a C to A substitution at nucleotide position 233, causing the proline (P) at amino acid position 78 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	0.0055	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T;D;D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.17
MutPred		0.23		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.84
MPC		0.11
ClinPred		0.44	T
GERP RS		4.1
Varity_R		0.12
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65664344;