20-14326127-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198391.3(FLRT3):c.1380A>C(p.Glu460Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 1,613,846 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.052 ( 328 hom., cov: 32)

Exomes 𝑓: 0.027 ( 787 hom. )

Consequence

FLRT3
NM_198391.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.162

Variant links:

Genes affected

FLRT3 (HGNC:3762): (fibronectin leucine rich transmembrane protein 3) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRTs may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. This gene is expressed in many tissues. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2010]

FLRT3 links:

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

MACROD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017079115).

BP6

Variant 20-14326127-T-G is Benign according to our data. Variant chr20-14326127-T-G is described in ClinVar as [Benign]. Clinvar id is 1259515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT3	NM_198391.3 link	c.1380A>C	p.Glu460Asp	missense_variant	Exon 3 of 3	ENST00000341420.5	NP_938205.1	Q9NZU0
MACROD2	NM_001351661.2 link	c.272-167352T>G		intron_variant	Intron 3 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT3	ENST00000341420.5 link	c.1380A>C	p.Glu460Asp	missense_variant	Exon 3 of 3	2	NM_198391.3	ENSP00000339912.4		Q9NZU0
MACROD2	ENST00000684519.1 link	c.272-167352T>G		intron_variant	Intron 3 of 17		NM_001351661.2	ENSP00000507484.1		A1Z1Q3-1

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

7904

AN:

152120

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0498

GnomAD3 exomes

AF:

0.0293

AC:

7338

AN:

250630

Hom.:

222

AF XY:

0.0272

AC XY:

3687

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0325

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0275

AC:

40122

AN:

1461608

Hom.:

787

Cov.:

AF XY:

0.0270

AC XY:

19598

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0327

Gnomad4 EAS exome

AF:

0.0202

Gnomad4 SAS exome

AF:

0.0162

Gnomad4 FIN exome

AF:

0.0304

Gnomad4 NFE exome

AF:

0.0256

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0520

AC:

7919

AN:

152238

Hom.:

328

Cov.:

AF XY:

0.0503

AC XY:

3745

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.0280

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0306

Hom.:

180

Bravo

AF:

0.0542

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.120

AC:

527

ESP6500EA

AF:

0.0248

AC:

213

ExAC

AF:

0.0315

AC:

3820

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0286

EpiControl

AF:

0.0246

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.9

DANN

Benign

0.81

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.78

.;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.48

N;N

REVEL

Benign

0.069

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.035

MutPred

0.25

Gain of catalytic residue at G459 (P = 0.0789);Gain of catalytic residue at G459 (P = 0.0789);

MPC

0.36

ClinPred

0.0021

GERP RS

2.6

Varity_R

0.050

gMVP

0.53

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