Variant 14-41887895-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000298119.9(LRFN5):c.1270G>A(p.Ala424Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRFN5
ENST00000298119.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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:

LRFN5 (HGNC:):

LRFN5 links:

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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=0.095615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN5	NM_152447.5 linkuse as main transcript	c.1270G>A	p.Ala424Thr	missense_variant	3/6	ENST00000298119.9	NP_689660.2	Q96NI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRFN5	ENST00000298119.9 linkuse as main transcript	c.1270G>A	p.Ala424Thr	missense_variant	3/6	1	NM_152447.5	ENSP00000298119.4	Q96NI6
LRFN5	ENST00000554171.1 linkuse as main transcript	c.1270G>A	p.Ala424Thr	missense_variant	5/7	1		ENSP00000451067.1	G3V364
LRFN5	ENST00000554120.5 linkuse as main transcript	c.1270G>A	p.Ala424Thr	missense_variant	3/4	5		ENSP00000451897.1	G3V4N1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000166

GnomAD4 genome

Cov.:

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

Apr 06, 2024

The c.1270G>A (p.A424T) alteration is located in exon 3 (coding exon 1) of the LRFN5 gene. This alteration results from a G to A substitution at nucleotide position 1270, causing the alanine (A) at amino acid position 424 to be replaced by a threonine (T). 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

0.086

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.026

T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.58

N;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.75

N;N;N

REVEL

Benign

0.017

Sift

Benign

0.48

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.066

B;.;B

Vest4

0.18

MutPred

0.26

Gain of glycosylation at A424 (P = 0.0865);Gain of glycosylation at A424 (P = 0.0865);Gain of glycosylation at A424 (P = 0.0865);

MVP

0.30

MPC

0.42

ClinPred

0.49

GERP RS

4.5

Varity_R

0.10

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over