NM_201412.3:c.1022G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201412.3(LUC7L):​c.1022G>A​(p.Arg341Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LUC7L
NM_201412.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.115089566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LUC7LNM_201412.3 linkc.1022G>A p.Arg341Gln missense_variant Exon 10 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.1022G>A p.Arg341Gln missense_variant Exon 10 of 10 1 NM_201412.3 ENSP00000293872.8 Q9NQ29-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461222
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
726874
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1022G>A (p.R341Q) alteration is located in exon 10 (coding exon 10) of the LUC7L gene. This alteration results from a G to A substitution at nucleotide position 1022, causing the arginine (R) at amino acid position 341 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
Benign
0.081
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.099
T;T
Eigen
Benign
-0.092
Eigen_PC
Benign
0.059
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.75
N;N
REVEL
Benign
0.050
Sift
Uncertain
0.029
D;D
Sift4G
Uncertain
0.044
D;T
Polyphen
0.016
B;.
Vest4
0.24
MutPred
0.17
Loss of MoRF binding (P = 0.0262);.;
MVP
0.39
MPC
0.65
ClinPred
0.74
D
GERP RS
5.1
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.074
gMVP
0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1268925301; hg19: chr16-239291; API