Variant 14-41891422-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152447.5(LRFN5):c.1558A>T(p.Met520Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,012 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

LRFN5
NM_152447.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

LRFN5 (HGNC:20360): (leucine rich repeat and fibronectin type III domain containing 5) This gene encodes a protein that belongs to the leucine-rich repeat and fibronectin type III domain-containing family of proteins. A similar protein in mouse, a glycosylated transmembrane protein, is thought to function in presynaptic differentiation. [provided by RefSeq, Sep 2016]

LRFN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2770717).

BS2

High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN5	NM_152447.5 linkuse as main transcript	c.1558A>T	p.Met520Leu	missense_variant	4/6	ENST00000298119.9	NP_689660.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRFN5	ENST00000298119.9 linkuse as main transcript	c.1558A>T	p.Met520Leu	missense_variant	4/6	1	NM_152447.5	ENSP00000298119	P3
LRFN5	ENST00000554171.1 linkuse as main transcript	c.1385+3412A>T		intron_variant		1		ENSP00000451067	A1
LRFN5	ENST00000554120.5 linkuse as main transcript	c.1385+3412A>T		intron_variant		5		ENSP00000451897	A1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000199

AC:

AN:

251462

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135906

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Nov 10, 2022

The c.1558A>T (p.M520L) alteration is located in exon 4 (coding exon 2) of the LRFN5 gene. This alteration results from a A to T substitution at nucleotide position 1558, causing the methionine (M) at amino acid position 520 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.022

Eigen

Benign

-0.10

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.021

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.38

REVEL

Benign

0.20

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.63

MutPred

0.47

Gain of sheet (P = 0.0827);

MVP

0.65

MPC

0.40

ClinPred

0.19

GERP RS

5.9

Varity_R

0.27

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over