NM_016019.5:c.316A>G

Variant names:

• chr7-139402197-A-G
• NM_016019.5:c.316A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016019.5(LUC7L2):​c.316A>G​(p.Lys106Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LUC7L2 NM_016019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.316A>G	p.Lys106Glu	missense	Exon 4 of 10	NP_057103.2	Q9Y383-1
	FMC1-LUC7L2	NM_001244584.3		c.514A>G	p.Lys172Glu	missense	Exon 5 of 11	NP_001231513.1
	LUC7L2	NM_001270643.2		c.313A>G	p.Lys105Glu	missense	Exon 5 of 11	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.316A>G	p.Lys106Glu	missense	Exon 4 of 10	ENSP00000347005.4	Q9Y383-1
	FMC1-LUC7L2	ENST00000541515.3	TSL:2	c.514A>G	p.Lys172Glu	missense	Exon 5 of 11	ENSP00000440222.1
	LUC7L2	ENST00000619796.4	TSL:1	c.313A>G	p.Lys105Glu	missense	Exon 5 of 11	ENSP00000483438.1	Q9Y383-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PhyloP100		9.3
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Benign	0.052	T
Sift4G	Benign	0.24	T
Polyphen		0.98	D
Vest4		0.68
MutPred		0.47		Loss of ubiquitination at K106 (P = 0.0077)
MVP		0.20
MPC		3.0
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.64
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr7-139086943;