7-139402197-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUC7L2	NM_016019.5	c.316A>G	p.Lys106Glu	missense_variant	Exon 4 of 10	ENST00000354926.9	NP_057103.2
FMC1-LUC7L2	NM_001244584.3	c.514A>G	p.Lys172Glu	missense_variant	Exon 5 of 11		NP_001231513.1
LUC7L2	NM_001270643.2	c.313A>G	p.Lys105Glu	missense_variant	Exon 5 of 11		NP_001257572.1
LUC7L2	NM_001244585.2	c.307A>G	p.Lys103Glu	missense_variant	Exon 5 of 11		NP_001231514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUC7L2	ENST00000354926.9	c.316A>G	p.Lys106Glu	missense_variant	Exon 4 of 10	1	NM_016019.5	ENSP00000347005.4
FMC1-LUC7L2	ENST00000541515.3	c.514A>G	p.Lys172Glu	missense_variant	Exon 5 of 11	2		ENSP00000440222.1

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

Jul 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316A>G (p.K106E) alteration is located in exon 4 (coding exon 4) of the LUC7L2 gene. This alteration results from a A to G substitution at nucleotide position 316, causing the lysine (K) at amino acid position 106 to be replaced by a glutamic acid (E). 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	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;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	.;.;L;.;.
PROVEAN	Uncertain	-2.4	N;.;N;.;N
REVEL	Benign	0.24
Sift	Benign	0.052	T;.;T;.;T
Sift4G	Benign	0.24	T;T;T;T;T
Polyphen		0.98, 0.99	.;D;D;.;.
Vest4		0.68
MutPred		0.47		.;.;Loss of ubiquitination at K106 (P = 0.0077);.;.;
MVP		0.20
MPC		3.0, 2.8
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-139086943;