7-139405765-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016019.5(LUC7L2):​c.488G>A​(p.Arg163Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LUC7L2
NM_016019.5 missense

Scores

3
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34711468).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LUC7L2NM_016019.5 linkuse as main transcriptc.488G>A p.Arg163Gln missense_variant 5/10 ENST00000354926.9 NP_057103.2 Q9Y383-1
FMC1-LUC7L2NM_001244584.3 linkuse as main transcriptc.686G>A p.Arg229Gln missense_variant 6/11 NP_001231513.1 Q96HJ9-2A0A0A6YYJ8
LUC7L2NM_001270643.2 linkuse as main transcriptc.485G>A p.Arg162Gln missense_variant 6/11 NP_001257572.1 Q9Y383-2
LUC7L2NM_001244585.2 linkuse as main transcriptc.479G>A p.Arg160Gln missense_variant 6/11 NP_001231514.1 Q9Y383-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LUC7L2ENST00000354926.9 linkuse as main transcriptc.488G>A p.Arg163Gln missense_variant 5/101 NM_016019.5 ENSP00000347005.4 Q9Y383-1
FMC1-LUC7L2ENST00000541515.3 linkuse as main transcriptc.686G>A p.Arg229Gln missense_variant 6/112 ENSP00000440222.1 A0A0A6YYJ8

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 13, 2023The c.488G>A (p.R163Q) alteration is located in exon 5 (coding exon 5) of the LUC7L2 gene. This alteration results from a G to A substitution at nucleotide position 488, causing the arginine (R) at amino acid position 163 to be replaced by a glutamine (Q). 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
Uncertain
0.53
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
.;.;T;.;.
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
.;D;D;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.35
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.4
.;.;L;.;.
PROVEAN
Uncertain
-2.8
D;.;D;.;D
REVEL
Benign
0.28
Sift
Benign
0.067
T;.;T;.;T
Sift4G
Uncertain
0.046
D;D;T;D;D
Polyphen
0.94, 0.95
.;P;P;.;.
Vest4
0.39
MutPred
0.50
.;.;Loss of MoRF binding (P = 0.0191);.;.;
MVP
0.47
MPC
2.6, 2.3
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr7-139090511; COSMIC: COSV54926455; API