3-3845558-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_020873.7(LRRN1):āc.917A>Gā(p.Tyr306Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
LRRN1
NM_020873.7 missense
NM_020873.7 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 4.75
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 -4 ACMG points.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRN1 | NM_020873.7 | c.917A>G | p.Tyr306Cys | missense_variant | 2/2 | ENST00000319331.4 | |
LRRN1 | NM_001324188.2 | c.917A>G | p.Tyr306Cys | missense_variant | 3/3 | ||
LRRN1 | NM_001324189.2 | c.917A>G | p.Tyr306Cys | missense_variant | 3/3 | ||
LRRN1 | XM_047448644.1 | c.917A>G | p.Tyr306Cys | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRN1 | ENST00000319331.4 | c.917A>G | p.Tyr306Cys | missense_variant | 2/2 | 1 | NM_020873.7 | P1 | |
SUMF1 | ENST00000448413.5 | c.1192-18049T>C | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250920Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135594
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461876Hom.: 0 Cov.: 74 AF XY: 0.00000138 AC XY: 1AN XY: 727240
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
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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 | May 18, 2023 | The c.917A>G (p.Y306C) alteration is located in exon 2 (coding exon 1) of the LRRN1 gene. This alteration results from a A to G substitution at nucleotide position 917, causing the tyrosine (Y) at amino acid position 306 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
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
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