16-190067-C-G

Variant summary

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

The NM_201412.3(LUC7L):​c.875G>C​(p.Arg292Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R292Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LUC7L
NM_201412.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.41
Variant links:
Genes affected
LUC7L (HGNC:6723): (LUC7 like) The LUC7L gene may represent a mammalian heterochromatic gene, encoding a putative RNA-binding protein similar to the yeast Luc7p subunit of the U1 snRNP splicing complex that is normally required for 5-prime splice site selection (Tufarelli et al., 2001 [PubMed 11170747]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

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=0.27437645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LUC7LNM_201412.3 linkc.875G>C p.Arg292Pro missense_variant Exon 9 of 10 ENST00000293872.13 NP_958815.1 Q9NQ29-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LUC7LENST00000293872.13 linkc.875G>C p.Arg292Pro missense_variant Exon 9 of 10 1 NM_201412.3 ENSP00000293872.8 Q9NQ29-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461422
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727034
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.17
T;.;.;T;.
Eigen
Benign
0.13
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.76
T;.;T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.27
T;T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.3
M;M;M;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.6
N;D;D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0050
D;T;T;T;T
Sift4G
Uncertain
0.028
D;D;D;T;D
Polyphen
0.0020
B;.;.;.;.
Vest4
0.47
MutPred
0.21
Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);.;.;
MVP
0.78
MPC
0.82
ClinPred
0.84
D
GERP RS
5.2
Varity_R
0.56
gMVP
0.39

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: chr16-240066; API