20-14326127-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLRT3	NM_198391.3	MANE Select	c.1380A>C	p.Glu460Asp	missense	Exon 3 of 3	NP_938205.1	Q9NZU0
MACROD2	NM_001351661.2	MANE Select	c.272-167352T>G		intron	N/A	NP_001338590.1	A1Z1Q3-1
FLRT3	NM_013281.4		c.1380A>C	p.Glu460Asp	missense	Exon 2 of 2	NP_037413.1	Q9NZU0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLRT3	ENST00000341420.5	TSL:2 MANE Select	c.1380A>C	p.Glu460Asp	missense	Exon 3 of 3	ENSP00000339912.4	Q9NZU0
FLRT3	ENST00000378053.3	TSL:1	c.1380A>C	p.Glu460Asp	missense	Exon 2 of 2	ENSP00000367292.3	Q9NZU0
MACROD2	ENST00000684519.1	MANE Select	c.272-167352T>G		intron	N/A	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

GnomAD2 exomes

AF:

0.0293

AC:

7338

AN:

250630

AF XY:

0.0272

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 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

African (AFR)

AF:

0.124

AC:

4156

AN:

33456

American (AMR)

AF:

0.0152

AC:

678

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0327

AC:

855

AN:

26114

East Asian (EAS)

AF:

0.0202

AC:

802

AN:

39686

South Asian (SAS)

AF:

0.0162

AC:

1395

AN:

86250

European-Finnish (FIN)

AF:

0.0304

AC:

1625

AN:

53400

Middle Eastern (MID)

AF:

0.0236

AC:

136

AN:

5760

European-Non Finnish (NFE)

AF:

0.0256

AC:

28447

AN:

1111866

Other (OTH)

AF:

0.0336

AC:

2028

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2507

5015

7522

10030

12537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1154

2308

3462

4616

5770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0520

AC:

7919

AN:

152238

Hom.:

328

Cov.:

AF XY:

0.0503

AC XY:

3745

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.120

AC:

4995

AN:

41544

American (AMR)

AF:

0.0236

AC:

361

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3468

East Asian (EAS)

AF:

0.0280

AC:

145

AN:

5174

South Asian (SAS)

AF:

0.0197

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0281

AC:

298

AN:

10614

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0260

AC:

1766

AN:

68000

Other (OTH)

AF:

0.0492

AC:

104

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

363

726

1090

1453

1816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0334

Hom.:

481

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.9

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.019

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

PhyloP100

0.16

PrimateAI

Benign

0.48

PROVEAN

Benign

0.48

REVEL

Benign

0.069

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.035

MutPred

0.25

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

Mutation Taster

=75/25

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over