3-3845131-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_020873.7(LRRN1):​c.490G>T​(p.Ala164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRRN1
NM_020873.7 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09137282).
BP6
Variant 3-3845131-G-T is Benign according to our data. Variant chr3-3845131-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2602154.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRN1NM_020873.7 linkuse as main transcriptc.490G>T p.Ala164Ser missense_variant 2/2 ENST00000319331.4 NP_065924.3
LRRN1NM_001324188.2 linkuse as main transcriptc.490G>T p.Ala164Ser missense_variant 3/3 NP_001311117.1
LRRN1NM_001324189.2 linkuse as main transcriptc.490G>T p.Ala164Ser missense_variant 3/3 NP_001311118.1
LRRN1XM_047448644.1 linkuse as main transcriptc.490G>T p.Ala164Ser missense_variant 2/2 XP_047304600.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRN1ENST00000319331.4 linkuse as main transcriptc.490G>T p.Ala164Ser missense_variant 2/21 NM_020873.7 ENSP00000314901 P1
SUMF1ENST00000448413.5 linkuse as main transcriptc.1192-17622C>A intron_variant, NMD_transcript_variant 2 ENSP00000404384

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250948
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461874
Hom.:
0
Cov.:
75
AF XY:
0.0000110
AC XY:
8
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 21, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
4.5
DANN
Benign
0.74
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.25
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.30
N
REVEL
Benign
0.052
Sift
Benign
1.0
T
Sift4G
Benign
0.82
T
Polyphen
0.0
B
Vest4
0.069
MVP
0.17
MPC
0.17
ClinPred
0.020
T
GERP RS
3.4
Varity_R
0.058
gMVP
0.16

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: rs371825663; hg19: chr3-3886815; API