chr3-3844734-G-C

Variant summary

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

The NM_020873.7(LRRN1):​c.93G>C​(p.Glu31Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LRRN1
NM_020873.7 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
Variant links:
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 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=0.17329252).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRN1NM_020873.7 linkuse as main transcriptc.93G>C p.Glu31Asp missense_variant 2/2 ENST00000319331.4
LRRN1NM_001324188.2 linkuse as main transcriptc.93G>C p.Glu31Asp missense_variant 3/3
LRRN1NM_001324189.2 linkuse as main transcriptc.93G>C p.Glu31Asp missense_variant 3/3
LRRN1XM_047448644.1 linkuse as main transcriptc.93G>C p.Glu31Asp missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRN1ENST00000319331.4 linkuse as main transcriptc.93G>C p.Glu31Asp missense_variant 2/21 NM_020873.7 P1
SUMF1ENST00000448413.5 linkuse as main transcriptc.1192-17225C>G intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
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 GeneticsJun 09, 2022The c.93G>C (p.E31D) alteration is located in exon 2 (coding exon 1) of the LRRN1 gene. This alteration results from a G to C substitution at nucleotide position 93, causing the glutamic acid (E) at amino acid position 31 to be replaced by an aspartic acid (D). 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
0.076
BayesDel_addAF
Benign
-0.023
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
16
DANN
Benign
0.81
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.027
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.12
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.15
N
REVEL
Benign
0.18
Sift
Benign
1.0
T
Sift4G
Benign
0.72
T
Polyphen
0.0010
B
Vest4
0.27
MutPred
0.27
Loss of disorder (P = 0.1429);
MVP
0.61
MPC
0.17
ClinPred
0.13
T
GERP RS
4.8
Varity_R
0.13
gMVP
0.38

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: chr3-3886418; API