Variant 14-41887619-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152447.5(LRFN5):c.994A>T(p.Thr332Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 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: 0.0000014 ( 0 hom. )

Consequence

LRFN5
NM_152447.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07997674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN5	NM_152447.5 linkuse as main transcript	c.994A>T	p.Thr332Ser	missense_variant	3/6	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.994A>T	p.Thr332Ser	missense_variant	3/6	1	NM_152447.5	ENSP00000298119	P3
LRFN5	ENST00000554171.1 linkuse as main transcript	c.994A>T	p.Thr332Ser	missense_variant	5/7	1		ENSP00000451067	A1
LRFN5	ENST00000554120.5 linkuse as main transcript	c.994A>T	p.Thr332Ser	missense_variant	3/4	5		ENSP00000451897	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000207

Hom.:

Bravo

AF:

0.00000378

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

Aug 28, 2023

The c.994A>T (p.T332S) alteration is located in exon 3 (coding exon 1) of the LRFN5 gene. This alteration results from a A to T substitution at nucleotide position 994, causing the threonine (T) at amino acid position 332 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.018

T;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.49

N;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.070

MutPred

0.52

Gain of disorder (P = 0.0379);Gain of disorder (P = 0.0379);Gain of disorder (P = 0.0379);

MVP

0.44

MPC

0.39

ClinPred

0.097

GERP RS

5.4

Varity_R

0.18

gMVP

0.18

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