7-139402197-AAA-GAG

Variant names:

• chr7-139402197-AAA-GAG
• NM_016019.5:c.316_318delAAAinsGAG
• LUC7L2 p.Lys106Glu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_016019.5(LUC7L2):​c.316_318delAAAinsGAG​(p.Lys106Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LUC7L2 NM_016019.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29
• Publications: 0 publications found

Genes affected

LUC7L2 (HGNC:21608): (LUC7 like 2, pre-mRNA splicing factor) This gene encodes a protein that contains a C2H2-type zinc finger, coiled-coil region and arginine, serine-rich (RS) domain. A similar protein in mouse interacts with sodium channel modifier 1, and the encoded protein may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

FMC1-LUC7L2 (HGNC:44671): (FMC1-LUC7L2 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring C7orf55 (chromosome 7 open reading frame 55) and LUC7L2 (LUC7-like 2) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016019.5. 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
	LUC7L2	NM_016019.5	MANE Select	c.316_318delAAAinsGAG	p.Lys106Glu	missense	N/A	NP_057103.2	Q9Y383-1
	FMC1-LUC7L2	NM_001244584.3		c.514_516delAAAinsGAG	p.Lys172Glu	missense	N/A	NP_001231513.1
	LUC7L2	NM_001270643.2		c.313_315delAAAinsGAG	p.Lys105Glu	missense	N/A	NP_001257572.1	Q9Y383-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUC7L2	ENST00000354926.9	TSL:1 MANE Select	c.316_318delAAAinsGAG	p.Lys106Glu	missense	N/A	ENSP00000347005.4	Q9Y383-1
	FMC1-LUC7L2	ENST00000541515.3	TSL:2	c.514_516delAAAinsGAG	p.Lys172Glu	missense	N/A	ENSP00000440222.1
	LUC7L2	ENST00000619796.4	TSL:1	c.313_315delAAAinsGAG	p.Lys105Glu	missense	N/A	ENSP00000483438.1	Q9Y383-2

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		9.3

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: chr7-139086943;