3-3845731-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_020873.7(LRRN1):c.1090C>T(p.Arg364Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
LRRN1
NM_020873.7 missense
NM_020873.7 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 5.97
Genes affected
LRRN1 (HGNC:20980): (leucine rich repeat neuronal 1) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794
BS2
High AC in GnomAdExome4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRN1 | NM_020873.7 | c.1090C>T | p.Arg364Cys | missense_variant | 2/2 | ENST00000319331.4 | NP_065924.3 | |
LRRN1 | NM_001324188.2 | c.1090C>T | p.Arg364Cys | missense_variant | 3/3 | NP_001311117.1 | ||
LRRN1 | NM_001324189.2 | c.1090C>T | p.Arg364Cys | missense_variant | 3/3 | NP_001311118.1 | ||
LRRN1 | XM_047448644.1 | c.1090C>T | p.Arg364Cys | missense_variant | 2/2 | XP_047304600.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRN1 | ENST00000319331.4 | c.1090C>T | p.Arg364Cys | missense_variant | 2/2 | 1 | NM_020873.7 | ENSP00000314901 | P1 | |
SUMF1 | ENST00000448413.5 | c.1192-18222G>A | intron_variant, NMD_transcript_variant | 2 | ENSP00000404384 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251042Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135648
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461866Hom.: 0 Cov.: 74 AF XY: 0.0000426 AC XY: 31AN XY: 727240
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
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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 submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.1090C>T (p.R364C) alteration is located in exon 2 (coding exon 1) of the LRRN1 gene. This alteration results from a C to T substitution at nucleotide position 1090, causing the arginine (R) at amino acid position 364 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at