Variant 11-92353662-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001367949.2(FAT3):c.1550T>C(p.Leu517Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00828 in 1,613,926 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 78 hom. )

Consequence

FAT3
NM_001367949.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010628939).

BP6

Variant 11-92353662-T-C is Benign according to our data. Variant chr11-92353662-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT3	NM_001367949.2 linkuse as main transcript	c.1550T>C	p.Leu517Ser	missense_variant	2/28	ENST00000525166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT3	ENST00000525166.6 linkuse as main transcript	c.1550T>C	p.Leu517Ser	missense_variant	2/28	5	NM_001367949.2		Q8TDW7-1
FAT3	ENST00000409404.6 linkuse as main transcript	c.1550T>C	p.Leu517Ser	missense_variant	1/25	5		P1	Q8TDW7-3

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

956

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00819

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00957

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00610

AC:

1516

AN:

248708

Hom.:

AF XY:

0.00611

AC XY:

824

AN XY:

134916

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00685

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00710

Gnomad NFE exome

AF:

0.00915

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.00849

AC:

12406

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

6045

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00739

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00672

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00770

GnomAD4 genome

AF:

0.00628

AC:

956

AN:

152300

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

443

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00819

Gnomad4 NFE

AF:

0.00957

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00862

Hom.:

Bravo

AF:

0.00612

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00239

AC:

ESP6500EA

AF:

0.00839

AC:

ExAC

AF:

0.00584

AC:

705

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00900

EpiControl

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FAT3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

FAT3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

0.095

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0050

N;.

MutationTaster

Benign

0.69

N;N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.9

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D

Vest4

0.87

MVP

0.83

ClinPred

0.047

GERP RS

5.8

Varity_R

0.21

gMVP

0.43

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