11-65893000-GA-CC

Variant names:

• chr11-65893000-GA-CC
• NM_005438.5:c.701_702delTCinsGG
• FOSL1 p.Val234Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005438.5(FOSL1):​c.701_702delTCinsGG​(p.Val234Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V234D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	NM_005438.5	MANE Select	c.701_702delTCinsGG	p.Val234Gly	missense	N/A	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.593_594delTCinsGG	p.Val198Gly	missense	N/A	NP_001287773.1	E9PPX2
	FOSL1	NM_001300856.2		c.503_504delTCinsGG	p.Val168Gly	missense	N/A	NP_001287785.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.701_702delTCinsGG	p.Val234Gly	missense	N/A	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.593_594delTCinsGG	p.Val198Gly	missense	N/A	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.698_699delTCinsGG	p.Val233Gly	missense	N/A	ENSP00000584051.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-65660471;