rs8120693

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198391.3(FLRT3):c.1129G>A(p.Ala377Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,912 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 24 hom., cov: 32)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

FLRT3
NM_198391.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.25

Publications

9 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=0.0016800463).

BP6

Variant 20-14326378-C-T is Benign according to our data. Variant chr20-14326378-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (2289/152224) while in subpopulation AFR AF = 0.0269 (1118/41552). AF 95% confidence interval is 0.0256. There are 24 homozygotes in GnomAd4. There are 1106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2289 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT3	NM_198391.3 link	c.1129G>A	p.Ala377Thr	missense_variant	Exon 3 of 3	ENST00000341420.5	NP_938205.1
MACROD2	NM_001351661.2 link	c.272-167101C>T		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.1129G>A	p.Ala377Thr	missense_variant	Exon 3 of 3	2	NM_198391.3	ENSP00000339912.4
MACROD2	ENST00000684519.1 link	c.272-167101C>T		intron_variant	Intron 3 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2290

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00907

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0110

AC:

2766

AN:

250884

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.00388

Gnomad EAS exome

AF:

0.00974

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0113

AC:

16555

AN:

1461688

Hom.:

118

Cov.:

AF XY:

0.0111

AC XY:

8090

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.0266

AC:

890

AN:

33462

American (AMR)

AF:

0.00573

AC:

256

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00360

AC:

AN:

26120

East Asian (EAS)

AF:

0.00673

AC:

267

AN:

39694

South Asian (SAS)

AF:

0.0116

AC:

1004

AN:

86258

European-Finnish (FIN)

AF:

0.00998

AC:

533

AN:

53420

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0115

AC:

12771

AN:

1111878

Other (OTH)

AF:

0.0110

AC:

665

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1099

2198

3296

4395

5494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.0150

AC:

2289

AN:

152224

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1106

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0269

AC:

1118

AN:

41552

American (AMR)

AF:

0.00747

AC:

114

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00909

AC:

AN:

5170

South Asian (SAS)

AF:

0.0114

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00970

AC:

103

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

744

AN:

68000

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

236

355

473

591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0117

Hom.:

Bravo

AF:

0.0151

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.0114

AC:

1388

Asia WGS

AF:

0.0150

AC:

AN:

3476

EpiCase

AF:

0.0107

EpiControl

AF:

0.00960

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign