Variant 14-41887041-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152447.5(LRFN5):c.416C>G(p.Ser139Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRFN5
NM_152447.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRFN5	NM_152447.5 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	3/6	ENST00000298119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRFN5	ENST00000298119.9 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	3/6	1	NM_152447.5	P3
LRFN5	ENST00000554171.1 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	5/7	1		A1
LRFN5	ENST00000554120.5 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	3/4	5		A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251260

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jan 03, 2022

The c.416C>G (p.S139C) alteration is located in exon 3 (coding exon 1) of the LRFN5 gene. This alteration results from a C to G substitution at nucleotide position 416, causing the serine (S) at amino acid position 139 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

D;D;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

-0.057

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.99

D;.;D

Vest4

0.38

MutPred

0.52

Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.39

MPC

1.2

ClinPred

0.87

GERP RS

5.6

Varity_R

0.73

gMVP

0.62

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.

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