Variant rs138676741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013280.5(FLRT1):c.1184C>T(p.Thr395Met) variant causes a missense change. The variant allele was found at a frequency of 0.0022 in 1,613,004 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0023 ( 3 hom. )

Consequence

FLRT1
NM_013280.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

FLRT1 links:

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MACROD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009934247).

BP6

Variant 11-64117451-C-T is Benign according to our data. Variant chr11-64117451-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461793.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT1	NM_013280.5 link	c.1184C>T	p.Thr395Met	missense_variant	3/3	ENST00000682287.1	NP_037412.2	Q9NZU1A0A6E1VY70
MACROD1	NM_014067.4 link	c.517+33788G>A		intron_variant		ENST00000255681.7	NP_054786.2	Q9BQ69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1 link	c.1184C>T	p.Thr395Met	missense_variant	3/3		NM_013280.5	ENSP00000507207.1		A0A6E1VY70
MACROD1	ENST00000255681.7 link	c.517+33788G>A		intron_variant		1	NM_014067.4	ENSP00000255681.6		Q9BQ69

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

255

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00151

AC:

378

AN:

249598

Hom.:

AF XY:

0.00170

AC XY:

230

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.00230

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00226

AC:

3296

AN:

1460626

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1595

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00260

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152378

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00177

AC:

215

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Peripheral neuropathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.067

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.79

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

REVEL

Benign

0.22

Sift

Benign

0.13

Sift4G

Uncertain

0.020

Vest4

0.34

MVP

0.61

MPC

0.81

ClinPred

0.026

GERP RS

5.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.2

gMVP

0.59

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